bluuebunny/crossref_metadata_2025_split huggingface dataset:
‘Fish’ (Actinopterygii andElasmobranchii) diversification patterns through deep time
Authors: Guinot Guillaume , Cavin Lionel 
Published: June 2015

ABSTRACTActinopterygii (ray‐finned fishes) andElasmobranchii (sharks, skates and rays) represent more than half of today's vertebrate taxic diversity (approximately 33000 species) and form the largest component of vertebrate diversity in extant aquatic ecosystems. Yet, patterns of ‘fish’ evolutionary history remain insufficiently understood and previous studies generally treated each group independently mainly because of their contrasting fossil record composition and corresponding sampling strategies. Because direct reading of palaeodiversity curves is affected by several biases affecting the fossil record, analytical approaches are needed to correct for these biases. In this review, we propose a comprehensive analysis based on comparison of large data sets related to competing phylogenies (including allRecent and fossil taxa) and the fossil record for both groups during theMesozoic–Cainozoic interval. This approach provides information on the ‘fish’ fossil record quality and on the corrected ‘fish’ deep‐time phylogenetic palaeodiversity signals, with special emphasis on diversification events. Because taxonomic information is preserved after analytical treatment, identified palaeodiversity events are considered both quantitatively and qualitatively and put within corresponding palaeoenvironmental and biological settings. Results indicate a better fossil record quality for elasmobranchs due to their microfossil‐like fossil distribution and their very low diversity in freshwater systems, whereas freshwater actinopterygians are diverse in this realm with lower preservation potential. Several important diversification events are identified at familial and generic levels for elasmobranchs, and marine and freshwater actinopterygians, namely in theEarly–MiddleJurassic (elasmobranchs),LateJurassic (actinopterygians),EarlyCretaceous (elasmobranchs, freshwater actinopterygians),Cenomanian (all groups) and thePaleocene–Eocene interval (all groups), the latter two representing the two most exceptional radiations among vertebrates. For each of these events along with theCretaceous‐Paleogene extinction, we provide an in‐depth review of the taxa involved and factors that may have influenced the diversity patterns observed. Among these, palaeotemperatures, sea‐levels, ocean circulation and productivity as well as continent fragmentation and environment heterogeneity (reef environments) are parameters that largely impacted on ‘fish’ evolutionary history, along with other biotic constraints.
Does the EarPopper® device improve hearing outcomes in children with persistent otitis media with effusion? A randomised single‐blinded controlled trial
Authors: Banigo A. , Hunt A. , Rourke T. , Whiteside O. , Aldren C. 
Published: June 2015

ObjectiveTo provide an independent evaluation of the efficacy and safety of the EarPopper® in improving hearing outcomes in children with otitis media with effusion (OME) and reducing the ventilation tube insertion rate.Study DesignRandomised single‐blinded controlled trial.SettingThe Ear Nose and Throat Department of a district general hospital (Heatherwood and Wexham Park).Participants and MethodsTwenty‐nine children aged between 4 and 11 years diagnosed with persistent OME lasting at least 3 months with an average hearing of 25 dBHL or worse in the better ear were randomised to a treatment or control group for 7 weeks using random computer‐generated codes. Syndromic children, children with developmental delay, previous grommets and cleft palate were excluded. The audiologists were blinded at the final post‐treatment audiogram.ResultsAfter the seven‐week period, the mean improvement in air conduction across all frequencies was 10.9 dBHL in the treatment group (P < 0.001) and 3.6 dBHL in the control group (P = 0.201). At every frequency, the treatment group had larger improvements in air conduction, the largest being at 4 kHz where the mean air conduction in both ears improved by 14.8 dBHL. Compliance with the EarPopper® was over 90%, the only side‐effect reported being discomfort in the ears immediately after use which resolved and did not affect compliance. The ventilation tube insertion rate was 53.3% in the treatment group and 78.6% in the control group. Median follow‐up time for all patients is 47.7 months.ConclusionOur study shows that the EarPopper® is a safe, effective treatment option for children with hearing loss from persistent OME, and it reduces the rate of ventilation tube insertion. More studies with larger sample sizes are required to support our findings.
Tricyclic antidepressants for the treatment of tenesmus associated with rectal prolapse
Authors: Livovsky D. M. , Adler S. N. , Adar T. , Bar‐Gil Shitrit A. , Lysy J. 
Published: June 2015

AbstractAimTenesmus in rectal prolapse leads to a vicious circle of straining with deterioration of prolapse. The primary phenomenon triggering this may be rectal hypersensitivity. We aimed to assess whether treatment with tricyclic antidepressants (TCAs) may break the vicious circle and improve tenesmus.MethodA retrospective review was carried out of patients with rectal prolapse and severe tenesmus who were poor surgical candidates or had refused surgery. They were treated at our tertiary centre with low dose tricyclic antidepressants.ResultsTwenty‐three (18 female) patients were included, with mean age 75.3 (±SD 14.6) years. The mean duration of symptoms was 10.8 (± 8.6) months. Full‐thickness rectal prolapse was diagnosed in 16 (70%) patients while seven (30%) had mucosal or incomplete prolapse. Ten (43%), eight (35%) and five (22%) patients were treated with nortriptyline (25 mg daily), amitriptyline (10 mg daily) and desipramine (25 mg daily). After a mean follow‐up of 9.05 (± 8.2) months, 14 (61%) patients reported significant improvement in symptoms, five (22%) had a partial response, three (13%) were lost to follow‐up and one (4%) failed to respond. The response rates for nortriptyline, desipramine and amitriptyline were 90%, 100% and 62.5%.ConclusionTo the best of our knowledge this is the first report to address the symptomatic, conservative treatment of tenesmus in patients with rectal prolapse. TCAs may be an acceptable option for poor surgical candidates or patients refusing surgery.
Taking Natural Limits Seriously: Implications for Development Studies and the Environment
Authors: Vira Bhaskar 
Published: June 2015

ABSTRACTThis article explores how thinking about ecological limits, thresholds and boundaries has evolved in the last few decades, and explores the analytical and political possibilities that emerge if development studies scholars engage with these ideas. It makes the case for an engaged political economy approach, which focuses on understanding how finite resources at a variety of scales are shared between the competing claims of different groups in society. The article suggests that, while the science of planetary limits is important, the most significant societal challenges are not about how close we are to the limits, but involve finding mechanisms to reconcile the difficult trade‐offs that inevitably arise when we consider alternative human pathways in the present and the future. Choices are ubiquitous, even when there may be no immediate ecological tipping point, and a political economy perspective focuses on the ways in which humanity prioritizes different, often irreconcilable, objectives and interests in relation to the environment. The productive consequence of this thinking for development studies is the need for a renewed focus on the key issues that define prosperity and well‐being, as well as the political and moral economy within which human society governs itself, and its relationships with nature.
Carbonic anhydrase inhibition blocks skeletogenesis and echinochrome production in Paracentrotus lividus and Heliocidaris tuberculata embryos and larvae
Authors: Zito Francesca , Koop Demian , Byrne Maria , Matranga Valeria 
Published: June 2015

Carbonic anhydrases (CAs) are a family of widely distributed metalloenzymes, involved in diverse physiological processes. These enzymes catalyse the reversible conversion of carbon dioxide to protons and bicarbonate. At least 19 genes encoding for CAs have been identified in the sea urchin genome, with one of these localized to the skeletogenic mesoderm (primary mesenchyme cells, PMCs). We investigated the effects of a specific inhibitor of CA, acetazolamide (AZ), on development of two sea urchin species with contrasting investment in skeleton production, Paracentrotus lividus and Heliocidaris tuberculata, to determine the role of CA on PMC differentiation, skeletogenesis and on non‐skeletogenic mesodermal (NSM) cells. Embryos were cultured in the presence of AZ from the blastula stage prior to skeleton formation and development to the larval stage was monitored. At the dose of 8 mmol/L AZ, 98% and 90% of P. lividus and H. tuberculata embryos lacked skeleton, respectively. Nevertheless, an almost normal PMC differentiation was indicated by the expression of msp130, a PMC‐specific marker. Strikingly, the AZ‐treated embryos also lacked the echinochrome pigment produced by the pigment cells, a subpopulation of NSM cells with immune activities within the larva. Conversely, all ectoderm and endoderm derivatives and other subpopulations of mesoderm developed normally. The inhibitory effects of AZ were completely reversed after removal of the inhibitor from the medium. Our data, together with new information concerning the involvement of CA on skeleton formation, provide evidence for the first time of a possible role of the CAs in larval immune pigment cells.
Targeted ultradeep next‐generation sequencing as a method for KITD816V mutation analysis in mastocytosis
Authors: Kristensen Thomas , Broesby‐Olsen Sigurd , Vestergaard Hanne , Bindslev‐Jensen Carsten , Møller Michael Boe ,   the Mastocytosis Centre Odense University Hospital (MastOUH)
Published: June 2015

AbstractNext‐generation sequencing (NGS) is becoming increasingly used for diagnostic mutation analysis in myeloid neoplasms and may also represent a feasible technique in mastocytosis. However, detection of the KIT D816V mutation requires a highly sensitive method in most patients due to the typically low mutation levels. In this study, we established an NGS‐based KIT mutation analysis and analyzed the sensitivity of D816V detection using the Ion Torrent platform. Eighty‐two individual NGS analyses were included in the study. All samples were also analyzed using highly sensitive KIT D816V mutation‐specific qPCR. Measurements of the background level in D816V‐negative samples supported a cutoff for positivity of 0.2% in three different NGS panels. Clinical samples from patients with SM that tested positive using qPCR with a D816V allele burden >0.2% also tested positive using NGS. Samples that tested positive using qPCR with an allele burden <0.2% tested negative using NGS. We thereby demonstrate that caution should be taken when using the potentially very sensitive NGS technique for KIT D816V mutation analysis in mastocytosis, as many patients with SM have D816V mutation levels below the detection limit of NGS. A dedicated and highly sensitive KIT D816V mutation analysis therefore remains important in mastocytosis diagnostics.
Direct‐acting oral anticoagulants: pharmacology, indications, management, and future perspectives
Authors: Gómez‐Outes Antonio , Suárez‐Gea Mª Luisa , Lecumberri Ramón , Terleira‐Fernández Ana Isabel , Vargas‐Castrillón Emilio 
Published: June 2015

AbstractIn recent years, several direct‐acting oral anticoagulants (DOAC) have become available for use in Europe and other regions in indications related to prophylaxis and treatment of venous and arterial thromboembolism. They include the oral direct thrombin inhibitor dabigatran etexilate (Pradaxa®, Boehringer Ingelheim) and the oral direct FXa inhibitors rivaroxaban (Xarelto®, Bayer HealthCare), apixaban (Eliquis®, Bristol‐Myers Squibb), and edoxaban (Lixiana®/Savaysa®, Daiichi‐Sankyo). The new compounds have a predictable dose response and few drug–drug interactions (unlike vitamin k antagonists), and they do not require parenteral administration (unlike heparins). However, they accumulate in patients with renal impairment, lack widely available monitoring tests for measuring its anticoagulant activity, and no specific antidotes for neutralization in case of overdose and/or severe bleeding are currently available. In this review, we describe the pharmacology of the DOAC, the efficacy, and safety data from pivotal studies that support their currently approved indications and discuss the postmarketing experience available. We also summarize practical recommendations to ensure an appropriate use of the DOAC according to existing data. Finally, we discuss relevant ongoing studies and future perspectives.
Computing reward‐prediction error: an integrated account of cortical timing and basal‐ganglia pathways for appetitive and aversive learning
Authors: Morita Kenji , Kawaguchi Yasuo 
Published: June 2015

AbstractThere are two prevailing notions regarding the involvement of the corticobasal ganglia system in value‐based learning: (i) the direct and indirect pathways of the basal ganglia are crucial for appetitive and aversive learning, respectively, and (ii) the activity of midbrain dopamine neurons represents reward‐prediction error. Although (ii) constitutes a critical assumption of (i), it remains elusive how (ii) holds given (i), with the basal‐ganglia influence on the dopamine neurons. Here we present a computational neural‐circuit model that potentially resolves this issue. Based on the latest analyses of the heterogeneous corticostriatal neurons and connections, our model posits that the direct and indirect pathways, respectively, represent the values of upcoming and previous actions, and up‐regulate and down‐regulate the dopamine neurons via the basal‐ganglia output nuclei. This explains how the difference between the upcoming and previous values, which constitutes the core of reward‐prediction error, is calculated. Simultaneously, it predicts that blockade of the direct/indirect pathway causes a negative/positive shift of reward‐prediction error and thereby impairs learning from positive/negative error, i.e. appetitive/aversive learning. Through simulation of reward‐reversal learning and punishment‐avoidance learning, we show that our model could indeed account for the experimentally observed features that are suggested to support notion (i) and could also provide predictions on neural activity. We also present a behavioral prediction of our model, through simulation of inter‐temporal choice, on how the balance between the two pathways relates to the subject's time preference. These results indicate that our model, incorporating the heterogeneity of the cortical influence on the basal ganglia, is expected to provide a closed‐circuit mechanistic understanding of appetitive/aversive learning.
Adolescent‐onset GABAAα1 silencing regulates reward‐related decision making
Authors: Butkovich Laura M. , DePoy Lauren M. , Allen Amanda G. , Shapiro Lauren P. , Swanson Andrew M. , Gourley Shannon L. 
Published: June 2015

AbstractThe GABAA receptor mediates fast, inhibitory signaling, and cortical expression of the α1 subunit increases during postnatal development. Certain pathological stimuli such as stressors or prenatal cocaine exposure can interfere with this process, but causal relationships between GABAAα1 deficiency and complex behavioral outcomes remain unconfirmed. We chronically reduced GABAAα1 expression selectively in the medial prefrontal cortex (prelimbic subregion) of mice using viral‐mediated gene silencing of Gabra1. Adolescent‐onset Gabra1 knockdown delayed the acquisition of a cocaine‐reinforced instrumental response but spared cocaine seeking in extinction and in a cue‐induced reinstatement procedure. To determine whether response acquisition deficits could be associated with impairments in action–outcome associative learning and memory, we next assessed behavioral sensitivity to instrumental contingency degradation. In this case, the predictive relationship between familiar actions and their outcomes is violated. Adolescent‐onset knockdown, although not adult‐onset knockdown, delayed the expression of goal‐directed response strategies in this task, resulting instead in inflexible habit‐like modes of response. Thus, the maturation of medial prefrontal cortex GABAAα1 systems during adolescence appears necessary for goal‐directed reward‐related decision making in adulthood. These findings are discussed in the light of evidence that prolonged Gabra1 deficiency may impair synaptic plasticity.
The retrotrapezoid nucleus stimulates breathing by releasing glutamate in adult conscious mice
Authors: Holloway Benjamin B. , Viar Kenneth E. , Stornetta Ruth L. , Guyenet Patrice G. 
Published: June 2015

AbstractThe retrotrapezoid nucleus (RTN) is a bilateral cluster of neurons located at the ventral surface of the brainstem below the facial nucleus. The RTN is activated by hypercapnia and stabilises arterial Pco2 by adjusting lung ventilation in a feedback manner. RTN neurons contain vesicular glutamate transporter‐2 (Vglut2) transcripts (Slc17a6), and their synaptic boutons are Vglut2‐immunoreactive. Here, we used optogenetics to test whether the RTN increases ventilation in conscious adult mice by releasing glutamate. Neurons located below the facial motor nucleus were transduced unilaterally to express channelrhodopsin‐2 (ChR2)–enhanced yellow fluorescent protein, with lentiviral vectors that employ the Phox2b‐activated artificial promoter PRSx8. The targeted population consisted of two types of Phox2b‐expressing neuron: non‐catecholaminergic neurons (putative RTN chemoreceptors) and catecholaminergic (C1) neurons. Opto‐activation of a mix of ChR2‐expressing RTN and C1 neurons produced a powerful stimulus frequency‐dependent (5–15 Hz) stimulation of breathing in control conscious mice. Respiratory stimulation was comparable in mice in which dopamine‐β‐hydroxylase (DβH)‐positive neurons no longer expressed Vglut2 (DβHCre/0;;Vglut2fl/fl). In a third group of mice, i.e. DβH+/+;;Vglut2fl/fl mice, we injected a mixture of PRSx8‐Cre lentiviral vector and Cre‐dependent ChR2 adeno‐associated virus 2 unilaterally into the RTN; this procedure deleted Vglut2 from ChR2‐expressing neurons regardless of whether or not they were catecholaminergic. The ventilatory response elicited by photostimulation of ChR2‐positive neurons was almost completely absent in these mice. Resting ventilatory parameters were identical in the three groups of mice, and their brains contained similar numbers of ChR2‐positive catecholaminergic and non‐catecholaminergic neurons. From these results, we conclude that RTN neurons increase breathing in conscious adult mice by releasing glutamate.
Can we use peripheral tissue biopsies to diagnose Parkinson's disease? A review of the literature
Authors: Schneider S. A. , Boettner M. , Alexoudi A. , Zorenkov D. , Deuschl G. , Wedel T. 
Published: June 2015

Phosphorylated α‐synuclein (phosαSYN) containing inclusions in neurons (Lewy bodies, LB) and nerve terminals (Lewy neurites, LN), the pathological hallmark of Parkinson's disease (PD), are not confined to the central nervous system, but have also been reported in peripheral tissues. However, the usefulness of αSYN/phosαSYN detection in tissues accessible to biopsies as a reliable biomarker for prodromal PD remains unclear. A systematic review of studies using biopsies of skin, olfactory and gastrointestinal (GI) tissues was conducted to evaluate the sensitivity and specificity of both αSYN and phosαSYN staining in PD patients. Data analysis was hampered by the diversity of the methods used, e.g. choice of biopsy sites, tissue processing, staining protocols and evaluation of the findings. Tissue obtained from GI tract/salivary glands (13 post‐mortem, 13 in vivo studies) yielded the highest overall sensitivity and specificity compared to skin (three post‐mortem, eight in vivo studies) and olfactory mucosa/bulb (six post‐mortem studies, one in vivo study). In contrast to phosαSYN, αSYN was more consistently detectable in peripheral tissues of healthy controls. GI tract/salivary glands appear to be the most promising candidate tissue for peripheral biopsy‐taking. phosαSYN is considered as the marker of choice to delineate pathological aggregates from normal αSYN regularly found in peripheral neural tissues. However, the sensitivity and specificity of phosαSYN are not yet acceptable for using phosαSYN as a reliable peripheral biomarker for PD in clinical routine. Further refinement regarding the interpretation of the peripheral αSYN/phosαSYN burden and the phenotypical definition of peripheral LB/LN is needed to optimize screening methods for prodromal PD.
Photoperiodic induction of prepupal diapause and its role in synchronization with host phenology in the hibiscus caterpillar, Xanthodes transversa
Authors: Shintani Yoshinori , Kawazu Kei , Hirose Yuzuru 
Published: June 2015

AbstractThe hibiscus caterpillar, Xanthodes transversa (Lepidoptera: Noctuidae), is a multivoltine insect that is an important pest of Malvaceae plants such as the okra, Abelmoschus esculentus, and the common rose mallow, Hibiscus mutabilis, in Japan. In the present study, the effects of photoperiod and temperature on the induction of prepupal diapause and the adaptive significance of this diapause were examined in a local population of X. transversa in Miyazaki, Kyushu, southwestern Japan. Larvae showed a long‐day photoperiodic response for controlling the induction of prepupal diapause with a critical day length between 13 and 14 h at 20 to 25°C. Under long‐day conditions larvae rapidly pupated from the sixth instar, but under short‐day conditions they entered diapause in the prepupal stage. Diapause occurrence in the field increased in late September, which was consistent with the laboratory results in terms of the photoperiodic response. Non‐diapause development after this time is maladaptive because most larvae of the next generation could not reach the critical stage (prepupae) before winter and died during early winter in outdoor experiments. Larvae suffered from a high rate of mortality when fed leaves collected late in autumn. The photoperiodic response for controlling the induction of diapause in this insect may play an important role in synchronizing the life cycle with the seasonal changes in food and temperature conditions.