bluuebunny/crossref_metadata_2025 huggingface dataset:
A dynamic mechanism for allosteric activation of Aurora kinase A by activation loop phosphorylation
Authors: Ruff Emily F. , Muretta Joseph M. , Thompson Andrew , Lake Eric , Cyphers Soreen , Albanese Steven K. , Hanson Sonya M. , Behr Julie M. , Thomas David D. , Chodera John D. , Levinson Nicholas M.
Published: October 2017

Many eukaryotic protein kinases are activated by phosphorylation on a specific conserved residue in the regulatory activation loop, a post-translational modification thought to stabilize the active DFG-In state of the catalytic domain. Here we use a battery of spectroscopic methods that track different catalytic elements of the kinase domain to show that the ~100-fold activation of the mitotic kinase Aurora A (AurA) by phosphorylation occurs without a population shift to the DFG-In state, and that the activation loop of the activated kinase remains highly dynamic. Instead, molecular dynamics simulations and electron paramagnetic resonance experiments show that phosphorylation profoundly alters the structure and dynamics of the DFG-In subpopulation, leading to activation of the kinase. Kinetics experiments tracking structural transitions during nucleotide binding suggest that a substantial DFG-Out subpopulation is an important feature of activated AurA that evolved to optimize the kinetics of substrate binding and product release.
Plasmodium vivax-like genome sequences shed new insights into Plasmodium vivax biology and evolution
Authors: Gilabert Aude , Otto Thomas D. , Rutledge Gavin G. , Franzon Blaise , Ollomo Benjamin , Arnathau Céline , Durand Patrick , Moukodoum Nancy D. , Okouga Alain-Prince , Ngoubangoye Barthélémy , Makanga Boris , Boudenga Larson , Paupy Christophe , Renaud François , Prugnolle Frank , Rougeron Virginie
Published: October 2017

Although Plasmodium vivax is responsible for the majority of malaria infections outside Africa, little is known about its evolution and pathway to humans. Its closest genetic relative, Plasmodium vivax-like, was discovered in African great apes and is hypothesized to have given rise to P. vivax in humans. To unravel the evolutionary history and adaptation of P. vivax, we generated using long and short read sequence technologies the two first P. vivax-like reference genomes and 9 additional P. vivax-like genotypes. Analyses show that the genomes of P. vivax and P. vivax-like are highly similar and co-linear within the core regions. Phylogenetic analyses clearly show that P. vivax-like parasites form a genetically distinct clade from P. vivax. Concerning the relative divergence dating, we show that the evolution of P. vivax in humans did not occur at the same time as the other human malaria agents, thus suggesting that the transfer of Plasmodium parasites to humans happened several times independently over the history of the Homo genus. We further identify several key genes that exhibit signatures of positive selection exclusively in the human P. vivax parasites. Interestingly, two of these genes have been identified to also be under positive selection in the other main human malaria agent, P. falciparum, thus suggesting their key role in the evolution of the ability of these parasites to infect humans or their anthropophilic vectors. We finally demonstrate that some gene families important for red blood cell (RBC) invasion (a key step of the life cycle of these parasites) have undergone lineage-specific evolution in the human parasite (e.g. Reticulocyte Binding Proteins).

Significance statements

Among the five species responsible for this malaria in humans, Plasmodium vivax is the most prevalent outside Africa and causes severe and incapacitating clinical symptoms with significant effects on human health. Its closest known relative was recently discovered in African great apes, Plasmodium vivax-like. This study aims to characterize the genome of the closest ape-relative to the human P. vivax parasite in order to get a better understanding of the evolution of this parasite.

A total of eleven P. vivax-like samples were obtained from infected chimpanzee blood samples and an infected Anopheles mosquito collected in Gabon. Through technical accomplishment and using short and long read sequence technologies, two newly genomes of P. vivax-like and further nine additional draft sequences were obtained. The genome-wide analyses performed provided new insights into the biology and adaptive evolution of P. vivax to different host species.
Genomic evidence of a widespread southern distribution during the Last Glacial Maximum for two eastern North American hickory species
Authors: Bemmels Jordan B. , Dick Christopher W.
Published: October 2017

Aim

Phylogeographic studies of temperate forest taxa often infer complex histories involving population subdivision into distinct refugia during the Last Glacial Maximum (LGM). However, temperate forests may have been broadly distributed in southeastern North America during the LGM. We investigate genome-wide genetic structure in two widespread eastern North America tree species to determine if range expansion from a contiguous area or from genetically isolated refugia better explains the postglacial history of trees and forests from this region.

Location

Eastern North America (ENA).

Taxa

Bitternut hickory (Carya cordiformis(Wangenh.) K.Koch) and shagbark hickory (Carya ovata(Mill.) K.Koch).

Methods

Genetic diversity and differentiation indices were calculated from >1,000 nuclear SNP loci genotyped in ca. 180 individuals per species sampled across ENA. Genetic structure was investigated using principle component analysis and genetic clustering algorithms. As an additional tool for inference, areas of suitable habitat during the LGM were predicted using species distribution models (SDMs).

Results

Populations across all latitudes showed similar levels of genetic diversity. Most genetic variation was weakly differentiated across ENA, with the exception of an outlier population ofCarya ovatain Texas. Genetic structure in each species exhibited an isolation-by-distance pattern. SDMs predicted high LGM habitat suitability over much of the southeastern United States.

Main conclusions

Both hickory species likely survived the LGM in a large region of continuous habitat and recolonized northern areas in a single expanding front that encountered few migration barriers. More complex scenarios, such as forest refugia, need not be invoked to explain genetic structure. The genetically distinct Texas population ofCarya ovatacould represent a separate glacial refugium, but other explanations are possible. Relative to that of other temperate forest regions, the phylogeographic history of ENA may have been exceptionally simple, involving a northward range shift but without well defined refugia.
Cooperative recruitment of Yan to paired high affinity ETS sites organizes repression to confer specificity and robustness to cardiac cell fate specification
Authors: Boisclair Lachance Jean-François , Webber Jemma L. , Rebay Ilaria
Published: October 2017

Cis regulatory elements (CREs) are defined by unique combinations of transcription factor binding sites. Emerging evidence suggests that the number, affinity and organization of sites play important roles in regulating enhancer output and ultimately gene expression. Here, we investigate how the cis-regulatory logic of a tissue-specific CRE responsible foreven-skipped(eve) induction during cardiogenesis organizes the competing inputs of two ETS members, the activator Pointed (Pnt) and the repressor Yan. Using a combination of reporter gene assays and CRISPR-Cas9 gene editing, we show that Yan and Pnt have distinct preferences for affinity of sites. Not only does Yan prefer high affinity sites, but a tandem pair of such sites is necessary and sufficient for Yan to tune Eve expression levels in newly specified cardioblasts and to block ectopic Eve induction and cell fate specification in surrounding progenitors. Mechanistically, the cooperative Yan recruitment promoted by this conserved high affinity ETS pair not only biases Yan-Pnt competition at the specific CRE, but also organizes Yan repressive complexes in 3D across theevelocus. Taken together our results uncover a novel mechanism by which differential interpretation of CRE syntax by a competing repressor-activator pair can confer both specificity and robustness to developmental transitions.
Copper(II) bis(4,4,4-trifluoro-1-phenylbutane-1,3-dionate) complexes with pyridin-2-one, 3-hydroxypyridine and 3-hydroxypyridin-2-one ligands: molecular structures and hydrogen-bonded networks
Authors: Perdih Franc
Published: October 2017

Copper(II) bis(4,4,4-trifluoro-1-phenylbutane-1,3-dionate) complexes with pyridin-2-one (pyon), 3-hydroxypyridine (hpy) and 3-hydroxypyridin-2-one (hpyon) were prepared and the solid-state structures of (pyridin-2-one-κO)bis(4,4,4-trifluoro-3-oxo-1-phenylbutan-1-olato-κ2
O,O′)copper(II), [Cu(C10H6F3O2)2(C5H5NO)] or [Cu(tfpb-κ2
O,O′)2(pyon-κO)], (I), bis(pyridin-3-ol-κO)bis(4,4,4-trifluoro-3-oxo-1-phenylbutan-1-olato-κ2
O,O′)copper(II), [Cu(C10H6F3O2)2(C5H5NO)2] or [Cu(tfpb-κ2
O,O′)2(hpy-κO)2], (II), and bis(3-hydroxypyridin-2-one-κO)bis(4,4,4-trifluoro-3-oxo-1-phenylbutan-1-olato-κ2
O,O′)copper(II), [Cu(C10H6F3O2)2(C5H5NO2)2] or [Cu(tfpb-κ2
O,O′)2(hpyon-κO)2], (III), were determined by single-crystal X-ray analysis. The coordination of the metal centre is square pyramidal and displays a rare example of a mutual cis arrangement of the β-diketonate ligands in (I) and a trans-octahedral arrangement in (II) and (III). Complex (II) presents the first crystallographic evidence of κO-monodentate hpy ligation to the transition metal enabling the pyridine N atom to participate in a two-dimensional hydrogen-bonded network through O—H...N interactions, forming a graph-set motif R
2
2(7) through a C—H...O interaction. Complex (III) presents the first crystallographic evidence of monodentate coordination of the neutral hpyon ligand to a metal centre and a two-dimensional hydrogen-bonded network is formed through N—H...O interactions facilitated by C—H...O interactions, forming the graph-set motifs R
2
2(8) and R
2
2(7).
Nogo Receptor crystal structures with a native disulfide pattern suggest a novel mode of self-interaction
Authors: Pronker Matti F. , Tas Roderick P. , Vlieg Hedwich C. , Janssen Bert J. C.
Published: October 2017

The Nogo Receptor (NgR) is a glycophosphatidylinositol-anchored cell-surface protein and is a receptor for three myelin-associated inhibitors of regeneration: myelin-associated glycoprotein, Nogo66 and oligodendrocyte myelin glycoprotein. In combination with different co-receptors, NgR mediates signalling that reduces neuronal plasticity. The available structures of the NgR ligand-binding leucine-rich repeat (LRR) domain have an artificial disulfide pattern owing to truncated C-terminal construct boundaries. NgR has previously been shown to self-associateviaits LRR domain, but the structural basis of this interaction remains elusive. Here, crystal structures of the NgR LRR with a longer C-terminal segment and a native disulfide pattern are presented. An additional C-terminal loop proximal to the C-terminal LRR cap is stabilized by two newly formed disulfide bonds, but is otherwise mostly unstructured in the absence of any stabilizing interactions. NgR crystallized in six unique crystal forms, three of which share a crystal-packing interface. NgR crystal-packing interfaces from all eight unique crystal forms are compared in order to explore how NgR could self-interact on the neuronal plasma membrane.
Can you put too much on your plate? Uncertainty exposure in servitized triads
Authors: Kreye Melanie E.
Published: October 2017

Purpose

Servitization increases the uncertainty exposure of provider firms due to the operational differences between services and production which is further increased when operations are set in triads. The purpose of this paper is to analyse the uncertainty exposure in servitized triads and explore suitable organisational responses.

Design/methodology/approach

A conceptual frame is defined detailing three uncertainty types (environmental, organisational and relational uncertainty) and suitable organisational responses to these. This frame guided the analysis of in-depth case evidence from a cross-national servitized triad in a European-North African set-up which was collected through 29 semi-structured interviews and secondary data.

Findings

The empirical study identified the existence of the three uncertainty types and directional knock-on effects between them. Specifically, environmental uncertainty created organisational uncertainty which in turn created relational uncertainty. The uncertainty types were reduced through targeted organisational responses where formal relational governance reduced environmental uncertainty, service capabilities reduced organisational uncertainty and informal relational governance reduced relational uncertainty. The knock-on effects were reduced through organisational and relational responses.

Originality/value

This paper makes two contributions. First, a structured analysis of the uncertainty exposure in servitized triads is presented which shows the existence of three individual uncertainty types and the knock-on effects between them. Second, organisational responses to reduce the three uncertainty types individually and the knock-on effects between them are presented.
E-procurement quality from an internal customer perspective
Authors: Brandon-Jones Alistair
Published: October 2017

Purpose

Despite significant investment in e-procurement by many organisations, perceived failings in the quality of such technologies and of the support provided to use them – termed here e-procurement quality – continue to generate resistance from internal customers who must assimilate e-procurement into their daily routines. Hence, the purpose of this paper is to advance the understanding of e-procurement quality from an internal customer perspective and to develop, refine, and validate construct measures.

Design/methodology/approach

Research was undertaken in the UK and the Netherlands incorporating a literature review, a qualitative study with 58 interviews, a quantitative study with 274 survey respondents, and a replication study with 154 survey respondents.

Findings

Analysis reveals that e-procurement quality comprises five universally applicable dimensions: processing, content, usability, professionalism, and training. A sixth dimension, specification, appears to be applicable, but context specific.

Originality/value

The study represents one of the most extensive investigations of e-procurement quality to date and is the first to examine its underlying dimensional structure. The multi-item scales developed and validated using a mixed-methods process are suitable for theory building and testing, as well as providing useful diagnostic value to practitioners.
Compassion focussed working in secure forensic care
Authors: Taylor Jon
Published: October 2017

Purpose

The purpose of this paper is to describe practices associated with compassion focussed therapy (CFT) in a secure forensic setting for men with a learning disability and personality disorder. The values of this model for both therapeutic work and the organisation of residential practices in a secure setting are considered.

Design/methodology/approach

The paper presents a conceptual discussion of the use of CFT with an offender population.

Findings

The paper describes the use of CFT as a framework for working with offenders with an intellectual disability and personality disorder. The paper discusses the organisation of service practices alongside more formal therapeutic interventions.

Practical implications

CFT offers a unique integrated model for working with offenders. The core CFT model invites staff teams to consider the safety seeking aspects of challenging behaviours and to understand these behaviours in the context of evolved threat processing mechanisms. The focus on emotional processing that is central to the model invites services to develop deep understanding of the functions of violence and other offending behaviours and to balance work in these areas alongside the development of capacities that offer individuals methods for effective emotional regulation.

Originality/value

The paper provides a unique discussion point for the organisation of forensic services for this population. The consideration of the wider social context of offender rehabilitation in terms of the residential settings, and the juxtaposition of this with formal treatments is rarely considered.
Making a splash
Authors: Sciulli Nick
Published: October 2017

Purpose

The purpose of this study is to investigate how accountability and transparency was used to inform the local community and support the decision-making of the Surf Coast Shire (SCS) with respect to the development of an aquatic and health centre.

Design/methodology/approach

This project investigates a case study of a proposed aquatic and leisure centre located within the SCS (Victoria-Australia). The paper draws on content analysis and an interpretative approach to critically analyse publicly available archival documents sourced from the SCS, consultant reports and the popular press.

Findings

Providing extensive disclosure for a major capital works project and engaging the community to determine support for such a project was undertaken for reasons of accountability and transparency. However, community feedback has provided evidence of divisions between and within local township communities.

Practical implications

This project illustrates that being transparent and communicating accounting information via different forums can create significant community engagement to facilitate council decision-making albeit at a cost to some social disharmony.

Originality/value

It is typical for local councils to prepare budgets that inform the community how funds will be expended. In this case, the council has sought feedback from the community before a capital-intensive decision has been made. This approach extends the notion of accountability by disclosing managements’ decision-making apparatus.
Dawn song in natural and artificial continuous day: Light pollution affects songbirds at high latitudes
Authors: Derryberry Elizabeth P.
Published: October 2017

In Focus: Da Silva, A., & Kempenaers, B. (2017). . Journal of Animal Ecology, 86, 1286–1297. doi: 10.1111/1365-2656.12739

Satellite images of the world at night show bright dots connected by glowing lines crisscrossing the globe. As these connect‐the‐dots become brighter and expand into more and more remote regions, much of the flora and fauna of the world are experiencing evolutionarily unprecedented levels of light at night. Light cues are essential to most physiological and behavioural processes, and so the need to measure the effects of light pollution on these processes is critical. In this issue, Da Silva and Kempenaers take on this task using an important reproductive behaviour in songbirds—dawn song. The geographic, temporal and taxonomic breadth of sampling in this study allows for a close examination of a potentially complex interaction between light pollution and natural variation in the behaviour of dawn singing across latitude, season and species. Their extensive dataset highlights complexity in how songbirds respond to light pollution. Although light pollution has a strong effect on the timing of dawn song, not all songbirds respond the same way to light pollution, and the effects of light pollution vary with changes in natural light levels. Early dawn singers show more flexibility in the timing of dawn song across the season and across latitudes than late dawn singers, and also appear less affected by light pollution at high latitudes than are late dawn singers. These findings suggest that not all songbirds are responding to artificial continuous daylight as they do to natural continuous daylight, highlighting the general need to measure the fitness effects of light pollution.
The Scottish Union Bill of 1656–7
Authors: Little Patrick
Published: October 2017

The Scottish Union Bill introduced to the second Protectorate Parliament in October 1656 was based on the union ordinance of 1654, but it was then subjected to wide‐ranging amendments over the next few months. These amendments made many concessions to the Scots, including recognizing their separate legal system and the rights of the burghs, and allowing an expansion of free trade. This article explores the implications of these changes to the constitutional relationship between the two nations, and identifies the changes with a programme of reform championed by the Scottish council, led by Lord Broghill. The fate of the Union Bill thus became linked to the wider reform movement that saw the replacement of the Instrument of Government with the more moderate, civilian constitution known as the Humble Petition and Advice in the spring of 1657.
Peers, Politics and the Price of Pepper: Skinner v. the East India Company
Authors: Paley Ruth
Published: October 2017

The case of Thomas Skinner v. the East India Company brought parliament to a standstill in 1668 in a confrontation between the Houses over their respective privileges that lasted nearly two years. There is no doubt that the case was exploited for political advantage by presbyterians anxious to block the passage of a new conventicles act, but that is far from being the whole story.  This article examines for the first time the details of the case and reliability of Skinner's claims against the East India Company.  It reveals that Thomas Skinner was somewhat of an obsessive fantasist who, far from being a presbyterian sympathiser, was close to the household of James, duke of York. At one stage his daughter was even reputed to be the mother of the ‘pretended’ prince of Wales. It concludes that Skinner was himself an unscrupulous opportunist, eager to exploit political and commercial uncertainty for private gain.
Comorbidity of Alcohol Use Disorder and Chronic Pain: Genetic Influences on Brain Reward and Stress Systems
Authors: Yeung Ellen W. , Craggs Jason G. , Gizer Ian R.
Published: October 2017

Alcohol use disorder (AUD) is highly comorbid with chronic pain (CP). Evidence has suggested that neuroadaptive processes characterized by reward deficit and stress surfeit are involved in the development of AUD and pain chronification. Neurological data suggest that shared genetic architecture associated with the reward and stress systems may contribute to the comorbidity of AUD and CP. This monograph first delineates the prevailing theories of the development of AUD and pain chronification focusing on the reward and stress systems. It then provides a brief summary of relevant neurological findings followed by an evaluation of evidence documented by molecular genetic studies. Candidate gene association studies have provided some initial support for the genetic overlap between AUD and CP; however, these results must be interpreted with caution until studies with sufficient statistical power are conducted and replications obtained. Genomewide association studies have suggested a number of genes (e.g., TBX19, HTR7, and ADRA1A) that are either directly or indirectly related to the reward and stress systems in the AUD and CP literature. Evidence reviewed in this monograph suggests that shared genetic liability underlying the comorbidity between AUD and CP, if present, is likely to be complex. As the advancement in molecular genetic methods continues, future studies may show broader central nervous system involvement in AUD–CP comorbidity.
Crowding as a primary source of stress in an endangered fragment‐dwelling strepsirrhine primate
Authors: Gabriel D. N. , Gould L. , Cook S.
Published: October 2017

Nutritional and social challenges arising from habitat fragmentation can be significant sources of stress for animals. If prolonged, such stressors can pose a threat to the longevity of a species within a fragmented landscape. While each may elicit a physiological response, the coupled and often additive nature of these stressors can make it difficult to determine their relative impact on an individual or population. We measured fecal glucocorticoids (fGC) in two populations of Lemur catta, an endangered strepsirrhine primate, inhabiting forest fragments that vary markedly in resource structure and population density. We also examined the relative importance of behavioral variables indicative of feeding environment, intergroup territoriality, and intragroup social interactions in predicting fGC levels in these populations. Lemur catta living with ample food resources but at high population density exhibited higher fGC concentrations throughout the study period, independent of sex or reproductive state. At both sites, fGC levels reflected consistent seasonal variation, with lowest levels occurring during the resource‐rich pre‐mating period. Foraging effort was positively associated with fGC levels at each site, yet the population exhibiting the highest foraging effort had consistently lower levels of fGC. Intergroup territoriality was a positive predictor and intragroup agonism a negative predictor of fGC levels; however, trends in these variables were inconsistent when examining the two sites separately. Within‐site group differences highlighted the additive nature of nutritional and social stressors in predicting fGC levels. Our results suggest that the intense or unpredictable impact of crowding and, correspondingly, heightened intergroup resource defense may be an important consideration when addressing long‐term conservation initiatives for fragment‐dwelling L. catta.
Beneficial effect of exogenous platelet factor 4 for detecting pathogenic heparin‐induced thrombocytopenia antibodies
Authors: Vayne Caroline , Guery Eve‐Anne , Kizlik‐Masson Claire , Rollin Jérôme , Bauters Anne , Gruel Yves , Pouplard Claire
Published: October 2017

The laboratory diagnosis of heparin‐induced thrombocytopenia (HIT) is based on an enzyme immunoassay combined with a functional test, and serotonin release assay (SRA) is the gold standard for detecting activating HIT antibodies. However, a recent atypical history of HIT prompted us to evaluate whether addition of platelet factor 4 (PF4) during SRA could improve its ability to detect pathogenic HIT antibodies. Using 5B9, a monoclonal antibody to PF4/H with a human Fc fragment, we first defined the optimal PF4 concentration for detecting low amounts of platelet‐activating IgG with SRA. Plasma samples from 50 patients with suspected HIT were then studied, and SRA was positive in 17 cases (Group SRApos), with relatively high levels of PF4‐specific IgG (median optical density = 2·66). SRA was also systematically performed after adding 10 μg/ml of PF4 in the reaction mixture, and significant serotonin release was measured with samples from 9 additional patients (Group PF4‐SRApos). Importantly, levels of PF4‐specific IgG were similar in these samples and those from the 24 persistently SRA negative patients. Moreover, the pre‐test probability of HIT was intermediate/high in all ‘SRApos’ or ‘SRA‐PF4pos’ patients. In conclusion, addition of exogenous PF4 might improve the detection of pathogenic HIT antibodies by SRA.
Lenalidomide and dexamethasone in patients with POEMS syndrome: results of a prospective, open‐label trial
Authors: Nozza Andrea , Terenghi Fabrizia , Gallia Francesca , Adami Fausto , Briani Chiara , Merlini Giampaolo , Giordano Laura , Santoro Armando , Nobile‐Orazio Eduardo
Published: October 2017

Given its anti‐angiogenic activity, lenalidomide may have a role in the treatment of POEMS (Peripheral neuropathy, Organomegaly, Endocrinopathy, Monoclonal plasma cell disorder and Skin changes) syndrome. This prospective, open‐label, pilot study evaluated the combination of lenalidomide + dexamethasone (RD) in 18 POEMS syndrome patients (13 pre‐treated, 5 newly‐diagnosed but ineligible for high‐dose therapy). Treatment consisted of six cycles of lenalidomide (25 mg/day for 21 days followed by 7 days rest) plus dexamethasone (40 mg/once a week). Patients responding after six cycles continued treatment until progression or unbearable toxicity. The primary endpoint was the proportion of patients with either neurological or clinical improvement. The RD combination was considered as deserving further evaluation if 9 of the first 15 patients responded. Ten responses were observed among the first 15 enrolled patients, meeting the primary endpoint. Fifteen of 18 patients (83%) completed six RD cycles: 13 (72%) patients responded and nine had both clinical and neurological improvement. Among the 15 patients who completed the six RD cycles, four were still on treatment after a 25‐month follow‐up. At 39 months of follow‐up, all patients were alive with a 3‐year progression‐free survival of 59%. No patient discontinued RD for toxicity. Overall, the RD regimen showed a high incidence of prolonged symptoms improvement and was well tolerated in most POEMS patients.
Recurrent cardiotoxicity potentiated by the interaction of proteasome inhibitor and immunomodulatory therapy for the treatment of multiple myeloma
Authors: Fradley Michael G. , Groarke John D. , Laubach Jacob , Alsina Melissa , Lenihan Daniel J. , Cornell Robert F. , Maglio Michelle , Shain Kenneth H. , Richardson Paul G. , Moslehi Javid
Published: October 2017

Patients with multiple myeloma (MM) have improved treatment options, including immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). Despite their efficacy, increased rates of cardiovascular (CV) complications occur in patients exposed to some of these therapies. While previous research has focused on identifying the toxicities inherent to each specific agent, the CV side effects may be potentiated by the combination of PIs and IMiDs plus dexamethasone. We present a patient with MM with recurrent cardiotoxicity only when exposed to combination PI and IMiD‐based therapy. We also review the literature in this context, and propose a potential algorithm for cardiotoxicity prevention in this population.
The wisdom of demagogues: institutions, corruption and support for authoritarian populists
Authors: Rohac Dalibor , Kumar Sahana , Johansson Heinö Andreas
Published: October 2017

This article analyses the drivers of support for authoritarian populist parties in Europe. Such parties claim to represent the interests of ordinary people against greedy and out‐of‐touch elites. Simultaneously, they reject conventional constraints on democratic policymaking. In recent years, such parties on the political left and right have been gaining influence in countries across Europe. Using a panel data set from 1980–2016, we use semiparametric Tobit models with country fixed effects to explain support for authoritarian populists. We find that large vote shares of right‐wing – but not left‐wing – authoritarian populists are associated closely to corruption. Other commonly cited explanations such as unemployment, inequality and immigration perform poorly in predicting support for populist political platforms on the political right. While a full theoretical explanation of the link between corruption and right‐wing populism remains beyond the scope of this article, we suggest that the mechanism involves political trust. Corruption weakens trust in political institutions, which populists exploit. Curbing the rise of right‐wing authoritarian populism in Europe will thus require restoring trust in the integrity of politics.
The impact of passive smoking on the risk of colorectal neoplasia in never, former, and current smokers
Authors: Jung Yoon Suk , Kim Nam Hee , Yang Hyo‐Joon , Park Soo‐Kyung , Park Jung Ho , Park Dong Il , Sohn Chong Il
Published: October 2017

Background and Aim

Active smoking is well known to be a risk factor for colorectal neoplasia (CRN). However, it remains unclear whether passive smoking is also related to the risk of CRN. This study investigated the effect of passive smoking on the risk of CRN in never, former, and current smokers.

Methods

A cross‐sectional study was performed on asymptomatic examinees who underwent colonoscopy as part of a health check‐up.

Results

Of 136 707 participants, 33 052 (24.2%) were never passive smokers, and 103 655 (75.8%) were ever passive smokers. The mean age of the study population was 41.0 years. The proportion of never, former, and current smokers was 56.9%, 21.4%, and 24.8%, respectively, and the proportion of overall CRN and advanced CRN (ACRN) was 15.4% and 1.7%, respectively. Ever passive smoke exposure was associated with an increased risk of overall CRN in never smokers (adjusted odds ratio [AOR] 1.08; 95% confidence interval [CI] 1.02–1.13) and former smokers (AOR 1.08; 95% CI 1.00–1.17) but not in current smokers (AOR 1.02; 95% CI 0.94–1.11). Additionally, it significantly increased the risk of ACRN among never smokers (AOR 1.17; 95% CI 1.01–1.35) and tended to increase the risk of ACRN among former smokers (AOR 1.26; 95% CI 0.99–1.61). Moreover, the risk of CRN increased with increasing frequency and duration of passive smoking in never and former smokers.

Conclusions

Passive smoking was an independent risk factor for CRN in never and former smokers. Never and former smokers who are highly exposed to passive smoke as well as current smokers should be given priority for colonoscopy.
Effect of the midazolam added with propofol‐based sedation in esophagogastroduodenoscopy: A randomized trial
Authors: Kim Eun Hye , Park Jun Chul , Shin Sung Kwan , Lee Yong Chan , Lee Sang Kil
Published: October 2017

Background and Aim

Although propofol has been widely used for sedation during esophagogastroduodenoscopy (EGD), adverse events including hypoxia and hypotension may be a concern in the propofol‐based sedation. We aimed to analyze whether administration of midazolam would improve safety and efficacy of propofol‐based sedation in EGD.

Methods

One hundred twenty patients who were scheduled to undergo diagnostic EGD were randomly assigned to either midazolam plus propofol (MP) or propofol alone groups. In the MP group, 2 mg of midazolam and 10 mg of propofol were given initially. In the propofol alone group, 40–60 mg of propofol was given initially. In both groups, 20 mg of propofol was given repeatedly to maintain moderate sedation as needed. Vital signs including oxygen saturation were monitored every 2 min. After the patients fully recovered, satisfaction score was investigated from endoscopists, nurses, and patients, respectively.

Results

The baseline characteristics did not differ between the MP and propofol alone groups. The mean required doses of propofol was (mean ± standard deviation) 0.3 ± 0.3 and 0.8 ± 0.2 mg/kg in the MP and propofol alone groups, respectively (P < 0.001). In addition, sedation‐related adverse events and recovery time did not differ between the two groups. The proportion of satisfactory did not differ between the two groups (MP vs propofol alone; proportion; patient, 95.0% vs 93.3%, P > 0.999; endoscopist, 73.3% vs 80.0%, P = 0.064; nurse, 73.3% vs 76.7%, P = 0.551).

Conclusion

Adding midazolam to propofol did not reduced the safety and efficacy, and sedation using propofol alone could be suitable for sedation during diagnostic EGD.
Retracted: Intra‐arterial transplantation of human bone marrow mesenchymal stem cells (hBMMSCs) improves behavioral deficits and alters gene expression in rodent stroke model
Authors: Vibhuti  , Khan Rehan , Sharma Alpana , Jain Suman , Mohanty Sujata , Prasad Kameshwar
Published: October 2017

Stroke is a multi‐factorial polygenic disease and is a major cause of death and adult disability. Administration of bone marrow stem cells protects ischemic rat brain by facilitating recovery of neurological functions. But the molecular mechanism of stem cells action and their effect on gene expression is not well explored. In this study, we have transplanted 1 × 106 human bone marrow mesenchymal stem cells (hBMMSCs) in middle cerebral artery occluded (MCAo) adult male Wistar rats through intracarotid artery route at 24 h after surgery. Motor behavioral tests (rotarod and open field) were performed to assess the changes in motor functions at day 0 and day1, 4, 8 and 14. The expression of studied genes at mRNA and protein level was quantified by using Q‐PCR and western blotting, respectively. Further, we have assessed the methylation pattern of promoter of these genes by using methylation‐specific PCR. Data were analyzed statistically and correlated. A significant improvement in behavioral deficits was observed in stem cells treated group after 14th day post stroke. Significantly (p < 0.05) increased mRNA and protein levels of brain derived neurotrophic factor and ANP genes in hBMMSCs treated group along with decrease in methylation level at their promoter was observed. On the other hand, significantly decreased mRNA and protein level of TSP1 and WNK1 in hBMMSCs treated group was observed. In conclusion, hBMMSCs administration significantly improves the behavioral deficits by improving motor and locomotor coordination. The promoter of TSP1 and WNK1 genes was found to be hyper‐methylated in hBMMSCs group resulting in their decreased expression while the promoter of ANP and brain derived neurotrophic factor was found to be hypo‐methylated. This study might shed a light on how hBMMSCs affect the gene expression by modulating methylation status.

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Epigenetic control of early neurodegenerative events in diabetic retinopathy by the histone deacetylase SIRT6
Authors: Zorrilla‐Zubilete María A. , Yeste Ada , Quintana Francisco J. , Toiber Debra , Mostoslavsky Raul , Silberman Dafne M.
Published: October 2017

Diabetic retinopathy (DR) is one of the common complications associated with diabetes mellitus and the leading cause of blindness worldwide. Recent research has demonstrated that DR is not only a microvascular disease but may be a result of neurodegenerative processes. Moreover, glucose‐induced neuron and glial cell damage may occur shortly after the onset of diabetes which makes the disease hard to diagnose at early stages. SIRT6, a NAD‐dependent sirtuin deacylase, modulates aging, energy metabolism, and neurodegeneration. In previous studies we showed that SIRT6 deficiency causes major retinal transmission defects, changes in the expression of glycolytic genes, and elevated levels of apoptosis. Given the importance of glucose availability for retinal function and the critical role of SIRT6 in modulating glycolysis, we aimed to analyze SIRT6 participation in the molecular machinery that regulates the development of experimental DR. Using non‐obese diabetic mice, we determined by western blot that 2 weeks after the onset of the disease, high glucose concentrations induced retinal increase in a neovascularization promoting factor (vascular endothelial growth factor, VEGF), and the loss of a neuroprotective factor (brain‐derived neurotrophic factor, BDNF) associated with reduced levels of SIRT6 and increased acetylation levels of its substrates (H3K9 and H3K56) suggesting a deregulation of key neural factors. Noteworthy, retinas from CNS conditionally deleted SIRT6 mice showed a resemblance to diabetic retinas exhibiting lower protein levels of BDNF factor and increased protein levels of VEGF. Moreover, cultured Müller glial cells subjected to high glucose concentrations exhibited decreased levels of SIRT6 and increased levels of H3K56 acetylation. In addition, the increment of VEGF levels induced by high glucose was reverted by the over‐expression of SIRT6 in this cell type. Accordingly, siRNA experiments showed that, when SIRT6 was silenced, VEGF levels increased. Our findings suggest that epigenetically regulated neurodegenerative events may occur at an early diabetic stage prior to the characteristic proliferative and vascular changes observed at a later diabetic stage.

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The use of emotional intelligence capabilities in clinical reasoning and decision‐making: A qualitative, exploratory study
Authors: Hutchinson Marie , Hurley John , Kozlowski Desirée , Whitehair Leeann
Published: October 2017

Aims and objectives

To explore clinical nurses’ experiences of using emotional intelligence capabilities during clinical reasoning and decision‐making.

Background

There has been little research exploring whether, or how, nurses employ emotional intelligence (EI) in clinical reasoning and decision‐making.

Design

Qualitative phase of a larger mixed‐methods study.

Methods

Semistructured qualitative interviews with a purposive sample of registered nurses (n = 12) following EI training and coaching. Constructivist thematic analysis was employed to analyse the narrative transcripts.

Results

Three themes emerged: the sensibility to engage EI capabilities in clinical contexts, motivation to actively engage with emotions in clinical decision‐making and incorporating emotional and technical perspectives in decision‐making.

Conclusion

Continuing to separate cognition and emotion in research, theorising and scholarship on clinical reasoning is counterproductive.

Relevance to clinical practice

Understanding more about nurses’ use of EI has the potential to improve the calibre of decisions, and the safety and quality of care delivered.
Risk assessment and subsequent nursing interventions in a forensic mental health inpatient setting: Associations and impact on aggressive behaviour
Authors: Maguire Tessa , Daffern Michael , Bowe Steven J , McKenna Brian
Published: October 2017

Aim and objectives

To examine associations between risk of aggression and nursing interventions designed to prevent aggression.

Background

There is scarce empirical research exploring the nature and effectiveness of interventions designed to prevent inpatient aggression. Some strategies may be effective when patients are escalating, whereas others may be effective when aggression is imminent. Research examining level of risk for aggression and selection and effectiveness of interventions and impact on aggression is necessary.

Design

Archival case file.

Methods

Data from clinical files of 30 male and 30 female patients across three forensic acute units for the first 60 days of hospitalisation were collected. Risk for imminent aggression as measured by the Dynamic Appraisal of Situational Aggression, documented nursing interventions following each assessment, and acts of aggression within the 24‐hours following assessment were collected. Generalised estimating equations were used to investigate whether intervention strategies were associated with reduction in aggression.

Results

When a Dynamic Appraisal of Situational Aggression assessment was completed, nurses intervened more frequently compared to days when no Dynamic Appraisal of Situational Aggression assessment was completed. Higher Dynamic Appraisal of Situational Aggression assessments were associated with a greater number of interventions. The percentage of interventions selected for males differed from females; males received more pro re nata medication and observation, and females received more limit setting, one‐to‐one nursing and reassurance. Pro re nata medication was the most commonly documented intervention (35.9%) in this study. Pro re nata medication, limit setting and reassurance were associated with an increased likelihood of aggression in some risk bands.

Conclusions

Structured risk assessment prompts intervention, and higher risk ratings result in more interventions. Patient gender influences the type of interventions. Some interventions are associated with increased aggression, although this depends upon gender and risk level.

Relevance to clinical practice

When structured risk assessments are used, there is greater likelihood of intervention. Intervention should occur early using least restrictive interventions.
Nurses’ perspectives on how an e‐message system supports cross‐sectoral communication in relation to medication administration: A qualitative study
Authors: Foged Signe , Nørholm Vibeke , Andersen Ove , Petersen Helle Vendel
Published: October 2017

Aims and objectives

To describe nurses’ perspectives on how an e‐message system supports communication between hospital and home care nurses in relation to medication administration.

Background

Medication administration is a complex process involving a high risk of error. Unclear communication and lack of updated information about medication have been identified as the leading cause of medication errors during care transitions. E‐message systems are progressively being used to improve information exchange across sectors, yet little is known about their usage for exchange of medication information between nurses.

Design

A qualitative design using content analysis.

Methods

Focus group interviews were conducted with nurses from eight hospital wards and six municipalities (n = 79). Participant observations were conducted in three hospital wards and in three municipalities (165 hr).

Results

The e‐message system did not provide the information needed by the home care nurses to ensure safe medication administration after discharge due to (1) limitations of the system, (2) hospital nurses’ lack of knowledge about home care nurses’ information needs and (3) hospital nurses’ lack of access to medication information. Due the home care nurses’ perception of responsibility, they bypassed the e‐message system to get the information.

Conclusions

The home care nurses perceived themselves as the last link in the safety chain. As such, access to adequate information was essential for the nurses to ensure safe medication administration; however, the e‐message system did not support exchange of the information needed.

Relevance to clinical practice

E‐message systems must meet home care nurses’ need for information to ensure that safe medication administration does not depend on the knowledge of the individual nurse. Moreover, other system factors that influence interprofessional collaboration and nurses’ cross‐sectoral communication must be addressed.
The ‘how’ and ‘where’ of plant microRNAs
Authors: Yu Yu , Jia Tianran , Chen Xuemei
Published: October 2017

MicroRNAs (miRNAs) are small non‐coding RNAs, of typically 20–24 nt, that regulate gene expression post‐transcriptionally through sequence complementarity. Since the identification of the first miRNA, lin‐4, in the nematode Caenorhabditis elegans in 1993, thousands of miRNAs have been discovered in animals and plants, and their regulatory roles in numerous biological processes have been uncovered. In plants, research efforts have established the major molecular framework of miRNA biogenesis and modes of action, and are beginning to elucidate the mechanisms of miRNA degradation. Studies have implicated restricted and surprising subcellular locations in which miRNA biogenesis or activity takes place. In this article, we summarize the current knowledge on how plant miRNAs are made and degraded, and how they repress target gene expression. We discuss not only the players involved in these processes, but also the subcellular sites in which these processes are known or implicated to take place. We hope to raise awareness that the cell biology of miRNAs holds the key to a full understanding of these enigmatic molecules.

Contents

Summary
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I.
MicroRNA biogenesis in plants
1002

II.
Modes of action of miRNAs
1007

III.
Turnover of miRNAs
1010

IV.
Concluding remarks
1013

Acknowledgements
1013

References
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