The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Coregulator Control of Androgen Receptor Action by a Novel Nuclear Receptor-Binding Motif

The androgen receptor (AR) is a ligand-activated transcription factor that is essential for prostate cancer development. It is activated by androgens through its ligand-binding domain (LBD), which consists predominantly of 11 α-helices. Upon ligand binding, the last helix is reorganized to an agonist conformation termed activator function-2 (AF-2) for coactivator binding. Several coactivators bind to the AF-2 pocket through conserved LXXLL or FXXLF sequences to enhance the activity of the receptor. Recently, a small compound-binding surface adjacent to AF-2 has been identified as an allosteric modulator of the AF-2 activity and is termed binding function-3 (BF-3). However, the role of BF-3 in vivo is currently unknown, and little is understood about what proteins can bind to it. Here we demonstrate that a duplicated GARRPR motif at the N terminus of the cochaperone Bag-1L functions through the BF-3 pocket. These findings are supported by the fact that a selective BF-3 inhibitor or mutations within the BF-3 pocket abolish the interaction between the GARRPR motif(s) and the BF-3. Conversely, amino acid exchanges in the two GARRPR motifs of Bag-1L can impair the interaction between Bag-1L and AR without altering the ability of Bag-1L to bind to chromatin. Furthermore, the mutant Bag-1L increases androgen-dependent activation of a subset of AR targets in a genome-wide transcriptome analysis, demonstrating a repressive function of the GARRPR/BF-3 interaction. We have therefore identified GARRPR as a novel BF-3 regulatory sequence important for fine-tuning the activity of the AR

Key Learning Outcomes for Clinical Pharmacology and Therapeutics Education in Europe: A Modified Delphi Study.

Harmonizing clinical pharmacology and therapeutics (CPT) education in Europe is necessary to ensure that the prescribing competency of future doctors is of a uniform high standard. As there are currently no uniform requirements, our aim was to achieve consensus on key learning outcomes for undergraduate CPT education in Europe. We used a modified Delphi method consisting of three questionnaire rounds and a panel meeting. A total of 129 experts from 27 European countries were asked to rate 307 learning outcomes. In all, 92 experts (71%) completed all three questionnaire rounds, and 33 experts (26%) attended the meeting. 232 learning outcomes from the original list, 15 newly suggested and 5 rephrased outcomes were included. These 252 learning outcomes should be included in undergraduate CPT curricula to ensure that European graduates are able to prescribe safely and effectively. We provide a blueprint of a European core curriculum describing when and how the learning outcomes might be acquired

Odour from horse chestnuts (Equus caballus) on toys increases playing time in Beagles

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Effects of diluent volume of a single dose of epidural bupivacaine in parturients during the first stage of labor

Background and Objectives. 0.1% bupivacaine for obstetric epidural analgesia is given by infusion, using a loading dose of a higher concentration alone or in combination with opioid analgesics. A single dose of 0.1% without any additive for relief of first-stage labor pain has not yet been documented. Methods. Fifty-eight primiparae in active labor and with less than 5 cm cervical dilatation received 20 mg epidural bupivacaine diluted in 4 mL [group 1: 0.5% (I)], 10 mL [group 2: 0.2% (II)], or 20 mL [group 3: 0.1% (III)]. Pain relief, dermatomal spread, and motor block were assessed. Results. Visual analog pain scale (VAS) was significantly lower in group 2 (0.88 ± 1.34) and group 3 (0.25 ± 0.61) than in group 1 (4.37 ± 2.57). Onset and time to maximum analgesia was significantly shorter in group 2 than in group 3. Mean duration of analgesia was 120 ± 21 minutes in group 3, 100 ± 26 in group 2, and 43 ± 21 in group 1. The mean numbers and upper limits of dermatomes blocked did not differ between groups 2 and 3, but were higher than in group 1. Motor blocks in groups 2 and 3 were more extensive than in group 1 with no difference between groups 2 and 3. Ten mL 0.2% or 20 mL 0.1% epidural bupivacaine results in a similar degree of pain relief, superior to that following 4 mL 0.5%, while duration was longest after 20 mL 0.1%. Conclusions. Analgesia lasts significantly longer following 20 mL 0.1% bupivacaine than following 10 mL 0.2% bupivacaine when given for first-stage labor pain. Four milliliters 0.5% bupivacaine results in inadequate pain relief.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Malignant hyperthermia suggestive hypermetabolic syndrome at emergence from anesthesia

A 6-year old female child received succinylcholine (1 mg.kg-1) and isoflurane (concentrations of 1.5-2 percent) and developed at the end of surgery a hypermetabolic syndrome suggestive of malignant hyperthermia (MH) with masseter muscle spasm, muscle rigidity, tachypnea, systolic hypertension (140 mmHg), tachycardia (205 beats.min-1), hypercarbia (end expiratory CO2 71 mmHg), and an increase in body temperature (39.2°C). The child responded well to therapy which included cooling, hyperventilation with pure oxygen and dantrolene administration. However, blood creatine kinase and myoglobin elevations were moderate (respectively 375 IU.L-1 and 114 μg.L-1) and an in vitro halothane and caffeine contracture test was negative. Differential diagnostic proposals are discussed and compared to the clinical incident.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

The Low Countries and Eastern Europe during the Cold War: Introduction

This introductory article critically assesses the main themes and issues that have dominated the historiography of the Low Countries and Eastern Europe during the Cold War. It reflects on the ways in which new archival sources and trends in international historical research can make the picture of East-West relations more diversified and complex in terms of actors, ideas, and directions. Rather than showing the importance and singularity of the Benelux countries as 'small states among big powers', it stresses transnational connections and perspectives, and dismantles some important premises with regards to these countries' position within the Cold War. In sum, this article wants to make clear that the Low Countries certainly deserve their place in Cold War historiography, not as a primus inter pares, but as an integral part of a wider transnational phenomenon with global but also often very local aspirations and dimensions.peerreview_statement: The publishing and review policy for this title is described in its Aims & Scope. aims_and_scope_url: http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=ydtc20status: publishe

The Benelux and the Cold War: Re-interpreting West-West Relations

© 2016 Taylor & Francis. What is there new to say on the Low Countries and transatlantic relations during the Cold War? How do recent trends in Cold War research open up uncharted areas to explore these relations from new angles and perspectives? With attention shifting to cultural, global, transnational and multi-centric approaches to the international history of the twentieth century, it would seem that the transatlantic is long passé as a primary frame of reference. As the first special issue in this series claimed (The Low Countries and Eastern Europe during the Cold War), existing scholarship on the Benelux nations has tended to emphasise the loyal ally thesis, the uniqueness of small states among larger powers and the importance of traditional diplomacy. With this special issue, a set of articles has been brought together that open up new ways to consider the changing relations both within and between the Benelux nations and their Western allies during the Cold War. As a starting point, it takes the dual approach of the Benelux nations as both actors in the Cold War and as sites where Cold War dynamics were played out and influenced local political and social outcomes. By applying such a structure-agency approach, new perspectives on the importance of the Cold War for Benelux history, and the relevance of the Benelux for Cold War history, can be mapped out.peerreview_statement: The publishing and review policy for this title is described in its Aims & Scope. aims_and_scope_url: http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=ydtc20status: publishe