bluuebunny/crossref_metadata_2025 huggingface dataset:
How to emerge from the conservatism in clinical research methodology?
Authors: Kotecki Nuria , Penel Nicolas , Awada Ahmad
Published: July 2017

Purpose of review

Despite recent changes in clinical research methodology, many challenges remain in drug development methodology.

Recent findings

Advances in molecular biology and cancer treatments have changed the clinical research landscape. Thus, we moved from empirical clinical oncology to molecular and immunological therapeutic approaches. Along with this move, adapted dose-limiting toxicities definitions, endpoints, and dose escalation methods have been proposed. Moreover, the classical frontier between phase I, phase II, and phase III has become unclear in particular for immunological approaches. So, investigators are facing major challenges in drug development methodology.

We propose to individualize clinical research using innovative approaches to significantly improve patient outcomes and targeting what is considered unmet need. Integrating high level of translational research and performing well designed biomarker studies with great potential for clinical practice are of utmost importance. This could be performed within new models of clinical research networks and by building a strong collaboration between academic, cooperative groups, on-site investigators, and pharma.
Dried Blood Spots Combined With Ultra–High-Performance Liquid Chromatography–Mass Spectrometry for the Quantification of the Antipsychotics Risperidone, Aripiprazole, Pipamperone, and Their Major Metabolites
Authors: Tron Camille , Kloosterboer Sanne M. , van der Nagel Bart C. H. , Wijma Rixt A. , Dierckx Bram , Dieleman Gwen C. , van Gelder Teun , Koch Birgit C. P.
Published: July 2017

Background:

Risperidone, aripiprazole, and pipamperone are antipsychotic drugs frequently prescribed for the treatment of comorbid behavioral problems in children with autism spectrum disorders. Therapeutic drug monitoring (TDM) could be useful to decrease side effects and to improve patient outcome. Dried blood spot (DBS) sample collection seems to be an attractive technique to develop TDM of these drugs in a pediatric population. The aim of this work was to develop and validate a DBS assay suitable for TDM and home sampling.

Methods:

Risperidone, 9-OH risperidone, aripiprazole, dehydroaripiprazole, and pipamperone were extracted from DBS and analyzed by ultra–high-performance liquid chromatography–tandem mass spectrometry using a C18 reversed-phase column with a mobile phase consisting of ammonium acetate/formic acid in water or methanol. The suitability of DBS for TDM was assessed by studying the influence of specific parameters: extraction solution, EDTA carryover, hematocrit, punching location, spot volume, and hemolysis. The assay was validated with respect to conventional guidelines for bioanalytical methods.

Results:

The method was linear, specific without any critical matrix effect, and with a mean recovery around 90%. Accuracy and imprecision were within the acceptance criteria in samples with hematocrit values from 30% to 45%. EDTA or hemolysis did not skew the results, and no punching carryover was observed. No significant influence of the spot volume or the punch location was observed. The antipsychotics were all stable in DBS stored 10 days at room temperature and 1 month at 4 or −80°C. The method was successfully applied to quantify the 3 antipsychotics and their metabolites in patient samples.

Conclusions:

A UHPLC-MS/MS method has been successfully validated for the simultaneous quantification of risperidone, 9-OH risperidone, aripiprazole, dehydroaripiprazole, and pipamperone in DBS. The assay provided good analytical performances for TDM and clinical research applications.
Consultation for Simple Laceration Repair When On-Call in the Emergency Department: Potential Quagmire
Authors: Zbar Ross I.S. , Monico Edward , Calise Arthur
Published: July 2017

What are the forces obligating a plastic surgeon who is on-call for the emergency department to respond to a consultation request for repair of a simple laceration? Although the duties are clear in cases of obvious surgical emergency, ambiguity and subsequent conflict may arise when the true nature of the emergency is less clear. Does the consultant’s clinical discretion dictate the obligation in the case of a simple laceration; or is it subservient to either the discretion of the requesting health-care provider or even the patient? Do federal statutes such as the Emergency Medical Treatment and Labor Act, or perhaps more local rules apply, such as the by-laws of the hospital? It would behoove all medical practitioners to familiarize themselves with both the legal and moral implications of these issues. Having legitimate policies in place which actively address those situations where the consultative obligation is unclear is critical to resolve potential conflict.
Genetics of paediatric cardiomyopathies
Authors: Ware Stephanie M.
Published: July 2017

Purpose of review

Paediatric cardiomyopathy is a rare disease with a genetic basis. The purpose of this review is to discuss the current status of genetic findings in the paediatric cardiomyopathy population and present recent progress in utilizing this information for management and therapy.

Recent findings

With increased clinical genetic testing, an understanding of the genetic causes of cardiomyopathy is improving and novel causes are identified at a rapid rate. Recent progress in identifying the scope of genetic variation in large population datasets has led to reassessment and refinement of our understanding of the significance of rare genetic variation. As a result, the stringency of variant interpretation has increased, at times leading to revision of previous mutation results. Transcriptome and epigenome studies are elucidating important pathways for disease progression and highlight similarities and differences in pathogenesis from adult cardiomyopathy. Therapy targeted towards the underlying cause of cardiomyopathy is emerging for a number of rare syndromes such as Pompe and Noonan syndromes, and genome editing and induced pluripotent stem cells provide promise for additional precision medicine approaches.

Genetics is moving at a rapid pace in paediatric cardiomyopathy. Genetic testing is increasingly being incorporated into clinical care. Although interpretation of rare genetic variation remains challenging, the opportunity to provide management and therapy targeted towards the underlying genetic cause is beginning to be realized.
Limits of stability in patients with vascular (due to diabetes) and nonvascular unilateral transtibial amputation: a cross-sectional study
Authors: Molina-Rueda Francisco , Molero-Sánchez Alberto , Carratalá-Tejada María , Cuesta-Gómez Alicia , Miangolarra-Page Juan C. , Alguacil-Diego Isabel M.
Published: July 2017

The aim of the study was to investigate the differences in the stability limits between patients with vascular and nonvascular unilateral transtibial amputation (UTA) and patients without amputation. Eighteen patients with UTA who used a prosthesis were divided into two groups: vascular (n=9) and nonvascular (n=9). Twenty-four patients without amputation served as the control group. Computerized dynamic posturography Smart EquiTest System, version 8.0 was used for measuring stability limits. The limits of stability test was used to assess the participants’ ability to voluntarily sway to various locations in space. The measured parameters were maximum centre of gravity (COG) excursion, endpoint COG excursion and directional control. Single-factor analysis of variance and Bonferroni adjustment a posteriori tests was performed to investigate the differences between groups. The patients with vascular UTA had significantly lower endpoint COG excursion to oblique and forward direction compared with controls (P=0.017). In addition, the patients with vascular UTA had significantly lower maximum COG excursion to oblique and forward and to oblique and backward directions (P=0.031; 0.019). Patients with vascular UTA had significantly lower endpoint and maximum COG excursion to oblique and backward direction compared with patients with nonvascular UTA (P=0.30; 0.029). To summarize, patients with vascular UTA have substantially reduced limits of stability compared with patients without amputation and the patients with nonvascular UTA.
Persistent pain in cancer survivors
Authors: Boland Elaine G. , Ahmedzai Sam H.
Published: July 2017

Purpose of review

As people are living longer after a diagnosis and primary treatment for cancer, or indeed living with cancer as a chronic disease, new problems are emerging in this growing population of so-called ‘survivors’. Persistent or chronic pain is one of the commonest complaints, arising from the tissue damage caused by the original neoplasm, consequences of surgery and other therapies, and – especially in older people – multimorbidity. This review explores some of the principle causes and mechanisms of this phenomenon and reviews the evidence for their management.

Recent findings

We review recent findings regarding persistent pain in adults after surgery, chemotherapy (including targeted biological therapies), hormone manipulation and radiation therapy; and osteonecrosis from corticosteroid treatment in children with cancer. Recent research has revealed some of the molecular, genetic, phenotypic and psychological factors that predispose some people to developing more persistent pain after cancer, and their long-term outcomes.

Although persistent pain in cancer patients surviving after primary treatment has been recognized for decades, only recently has research shown how this arises and some possible ways to intervene by prevention and interventions. New holistic models for management of persistent cancer-related pain are needed.
Quantitative Evaluation of the Impact of Ethylenediaminetetraacetic Acid Pretreatment on Single-Antigen Bead Assay
Authors: Liu Chang , Pang Sue , Phelan Donna , Brennan Daniel C. , Mohanakumar Thalachallour
Published: July 2017

Background

Ethylenediaminetetraacetic acid (EDTA) pretreatment has been shown to overcome complement interference in the single-antigen bead (SAB) assay. However, a quantitative evaluation of its impact on the assay for preemptive application to diverse clinical samples is still lacking.

Methods

Serum samples from 95 renal transplant candidates were tested with and without EDTA-pretreatment in parallel. Changes in mean fluorescence intensity (MFI) values were analyzed to determine the impact of EDTA-pretreatment and the characteristics of complement interference.

Results

MFI values from EDTA-treated and untreated sera showed good correlations (r = 0.99) and were linear after excluding outliers (slopes, 1; intercepts, −63.7 and −24.2 for class I and II, respectively). Using an assay cutoff of 2000 MFI, positive/negative assignments were concordant for 99% of the 9215 class I beads and 9025 class II beads tested. As defined by an MFI increment above 4000 after EDTA pretreatment, complement interference affected 172 class I beads in 12 samples (12.6%) and 60 class II beads in 7 samples (7.4%), and the findings were supported in 83% and 86% of these samples by dilution studies. In a case study, EDTA pretreatment prevented falsely low MFI values and facilitated the interpretation of titration curves. Finally, EDTA pretreatment reduced the coefficient of variance (CV) by 2.1% and 2.4% for class I and II beads respectively (P < 0.0001).

Conclusions

It is safe to preemptively treat all clinical samples with EDTA before SAB assay to prevent false negative results or falsely low MFI values. EDTA pretreatment has the added benefit of improved assay precision.
Taking chances and making mistakes: non-genetic phenotypic heterogeneity and its consequences for surviving in dynamic environments
Authors: van Boxtel Coco , van Heerden Johan H. , Nordholt Niclas , Schmidt Phillipp , Bruggeman Frank J.
Published: July 2017

Natural selection has shaped the strategies for survival and growth of microorganisms. The success of microorganisms depends not only on slow evolutionary tuning but also on the ability to adapt to unpredictable changes in their environment. In principle, adaptive strategies range from purely deterministic mechanisms to those that exploit the randomness intrinsic to many cellular and molecular processes. Depending on the environment and selective pressures, particular strategies can lie somewhere along this continuum. In recent years, non-genetic cell-to-cell differences have received a lot of attention, not least because of their potential impact on the ability of microbial populations to survive in dynamic environments. Using several examples, we describe the origins of spontaneous and induced mechanisms of phenotypic adaptation. We identify some of the commonalities of these examples and consider the potential role of chance and constraints in microbial phenotypic adaptation.
Remotely sensed wind speed predicts soaring behaviour in a wide-ranging pelagic seabird
Authors: Gibb Rory , Shoji Akiko , Fayet Annette L. , Perrins Chris M. , Guilford Tim , Freeman Robin
Published: July 2017

Global wind patterns affect flight strategies in many birds, including pelagic seabirds, many of which use wind-powered soaring to reduce energy costs during at-sea foraging trips and migration. Such long-distance movement patterns are underpinned by local interactions between wind conditions and flight behaviour, but these fine-scale relationships are far less well understood. Here we show that remotely sensed ocean wind speed and direction are highly significant predictors of soaring behaviour in a migratory pelagic seabird, the Manx shearwater (
Puffinus puffinus
). We used high-frequency GPS tracking data (10 Hz) and statistical behaviour state classification to identify two energetic modes in at-sea flight, corresponding to flap-like and soar-like flight. We show that soaring is significantly more likely to occur in tailwinds and crosswinds above a wind speed threshold of around 8 m s
−1
, suggesting that these conditions enable birds to reduce metabolic costs by preferentially soaring over flapping. Our results suggest a behavioural mechanism by which wind conditions may shape foraging and migration ecology in pelagic seabirds, and thus indicate that shifts in wind patterns driven by climate change could impact this and other species. They also emphasize the emerging potential of high-frequency GPS biologgers to provide detailed quantitative insights into fine-scale flight behaviour in free-living animals.
Range contractions of the world's large carnivores
Authors: Wolf Christopher , Ripple William J.
Published: July 2017

The majority of the world's terrestrial large carnivores have undergone substantial range contractions and many of these species are currently threatened with extinction. However, there has been little effort to fully quantify the extent of large carnivore range contractions, which hinders our ability to understand the roles and relative drivers of such trends. Here we present and analyse a newly constructed and comprehensive set of large carnivore range contraction maps. We reveal the extent to which ranges have contracted since historical times and identify regions and biomes where range contractions have been particularly large. In summary, large carnivores that have experienced the greatest range contractions include the red wolf (
Canis rufus
) (greater than 99%), Ethiopian wolf (
Canis simensis
) (99%), tiger (
Panthera tigris
) (95%) and lion (
Panthera leo
) (94%). In general, the greatest range contractions occurred in Southeastern Asia and Africa. Motivated by the ecological importance of intact large carnivore guilds, we also examined the spatial extent of intact large carnivore guilds both for the entire world and regionally. We found that intact carnivore guilds occupy just 34% of the world's land area. This compares to 96% in historic times. Spatial modelling of range contractions showed that contractions were significantly more likely in regions with high rural human population density, cattle density or cropland. Our results offer new insights into how best to prevent further range contractions for the world's largest carnivores, which will assist efforts to conserve these species and their important ecological effects.
Individual-level movement bias leads to the formation of higher-order social structure in a mobile group of baboons
Authors: Bonnell Tyler R. , Clarke Parry M. , Henzi S. Peter , Barrett Louise
Published: July 2017

In mobile social groups, influence patterns driving group movement can vary between democratic and despotic. The arrival at any single pattern of influence is thought to be underpinned by both environmental factors and group composition. To identify the specific patterns of influence driving travel decision-making in a chacma baboon troop, we used spatially explicit data to extract patterns of individual movement bias. We scaled these estimates of individual-level bias to the level of the group by constructing an influence network and assessing its emergent structural properties. Our results indicate that there is heterogeneity in movement bias: individual animals respond consistently to particular group members, and higher-ranking animals are more likely to influence the movement of others. This heterogeneity resulted in a group-level network structure that consisted of a single core and two outer shells. Here, the presence of a core suggests that a set of highly interdependent animals drove routine group movements. These results suggest that heterogeneity at the individual level can lead to group-level influence structures, and that movement patterns in mobile social groups can add to the exploration of both how these structures develop (i.e. mechanistic aspects) and what consequences they have for individual- and group-level outcomes (i.e. functional aspects).
Integrating sentiment and social structure to determine preference alignments: the Irish Marriage Referendum
Authors: O’Sullivan David J. P. , Garduño-Hernández Guillermo , Gleeson James P. , Beguerisse-Díaz Mariano
Published: July 2017

We examine the relationship between social structure and sentiment through the analysis of a large collection of tweets about the Irish Marriage Referendum of 2015. We obtain the sentiment of every tweet with the hashtags#marrefand#marriagerefthat was posted in the days leading to the referendum, and construct networks to aggregate sentiment and use it to study the interactions among users. Our analysis shows that the sentiment of outgoing mention tweets is correlated with the sentiment of incoming mentions, and there are significantly more connections between users with similar sentiment scores than among users with opposite scores in the mention and follower networks. We combine the community structure of the follower and mention networks with the activity level of the users and sentiment scores to find groups that support voting ‘yes’ or ‘no’ in the referendum. There were numerous conversations between users on opposing sides of the debate in the absence of follower connections, which suggests that there were efforts by some users to establish dialogue and debate across ideological divisions. Our analysis shows that social structure can be integrated successfully with sentiment to analyse and understand the disposition of social media users around controversial or polarizing issues. These results have potential applications in the integration of data and metadata to study opinion dynamics, public opinion modelling and polling.
Fire ants perpetually rebuild sinking towers
Authors: Phonekeo Sulisay , Mlot Nathan , Monaenkova Daria , Hu David L. , Tovey Craig
Published: July 2017

In the aftermath of a flood, fire ants,
Solenopsis invicta
, cluster into temporary encampments. The encampments can contain hundreds of thousands of ants and reach over 30 ants high. How do ants build such tall structures without being crushed? In this combined experimental and theoretical study, we investigate the shape and rate of construction of ant towers around a central support. The towers are bell shaped, consistent with towers of constant strength such as the Eiffel tower, where each element bears an equal load. However, unlike the Eiffel tower, the ant tower is built through a process of trial and error, whereby failed portions avalanche until the final shape emerges. High-speed and novel X-ray videography reveal that the tower constantly sinks and is rebuilt, reminiscent of large multicellular systems such as human skin. We combine the behavioural rules that produce rafts on water with measurements of adhesion and attachment strength to model the rate of growth of the tower. The model correctly predicts that the growth rate decreases as the support diameter increases. This work may inspire the design of synthetic swarms capable of building in vertical layers.
Direct linearizing transform for three-dimensional discrete integrable systems: the lattice AKP, BKP and CKP equations
Authors: Fu Wei , Nijhoff Frank W.
Published: July 2017

A unified framework is presented for the solution structure of three-dimensional discrete integrable systems, including the lattice AKP, BKP and CKP equations. This is done through the so-called direct linearizing transform, which establishes a general class of integral transforms between solutions. As a particular application, novel soliton-type solutions for the lattice CKP equation are obtained.
Walking like an ant: a quantitative and experimental approach to understanding locomotor mimicry in the jumping spiderMyrmarachne formicaria
Authors: Shamble Paul S. , Hoy Ron R. , Cohen Itai , Beatus Tsevi
Published: July 2017

Protective mimicry, in which a palatable species avoids predation by being mistaken for an unpalatable model, is a remarkable example of adaptive evolution. These complex interactions between mimics, models and predators can explain similarities between organisms beyond the often-mechanistic constraints typically invoked in studies of convergent evolution. However, quantitative studies of protective mimicry typically focus on static traits (e.g. colour and shape) rather than on dynamic traits like locomotion. Here, we use high-speed cameras and behavioural experiments to investigate the role of locomotor behaviour in mimicry by the ant-mimicking jumping spiderMyrmarachne formicaria, comparing its movement to that of ants and non-mimicking spiders. Contrary to previous suggestions, we find mimics walk using all eight legs, raising their forelegs like ant antennae only when stationary. Mimics exhibited winding trajectories (typical wavelength = 5–10 body lengths), which resemble the winding patterns of ants specifically engaged in pheromone-trail following, although mimics walked on chemically inert surfaces. Mimics also make characteristically short (approx. 100 ms) pauses. Our analysis suggests that this makes mimics appear ant-like to observers with slow visual systems. Finally, behavioural experiments with predatory spiders yield results consistent with the protective mimicry hypothesis. These findings highlight the importance of dynamic behaviours and observer perception in mimicry.
Consistent cooperation in a cichlid fish is caused by maternal and developmental effects rather than heritable genetic variation
Authors: Kasper Claudia , Kölliker Mathias , Postma Erik , Taborsky Barbara
Published: July 2017

Studies on the evolution of cooperative behaviour are typically confined to understanding its adaptive value. It is equally essential, however, to understand its potential to evolve, requiring knowledge about the phenotypic consistency and genetic basis of cooperative behaviour. While previous observational studies reported considerably high heritabilities of helping behaviour in cooperatively breeding vertebrates, experimental studies disentangling the relevant genetic and non-genetic components of cooperative behaviour are lacking. In a half-sibling breeding experiment, we investigated the repeatability and heritability of three major helping behaviours performed by subordinates of the cooperatively breeding fishNeolamprologus pulcher. To experimentally manipulate the amount of help needed in a territory, we raised the fish in two environments differing in egg predation risk. All three helping behaviours were significantly repeatable, but had very low heritabilities. The high within-individual consistencies were predominantly due to maternal and permanent environment effects. The perceived egg predation risk had no effect on helping, but social interactions significantly influenced helping propensities. Our results reveal that developmentally plastic adjustments of provided help to social context shape cooperative phenotypes, whereas heritable genetic variation plays a minor role.
Spatial storage effect promotes biodiversity during adaptive radiation
Authors: Tan Jiaqi , Rattray Jennifer B. , Yang Xian , Jiang Lin
Published: July 2017

Many ecological communities are enormously diverse. Variation in environmental conditions over time and space provides opportunities for temporal and spatial storage effects to operate, potentially promoting species coexistence and biodiversity. While several studies have provided empirical evidence supporting the significance of the temporal storage effect for coexistence, empirical tests of the role of the spatial storage effect are rare. In particular, we know little about how the spatial storage effect contributes to biodiversity over evolutionary timescales. Here, we report the first experimental study on the role of the spatial storage effect in the maintenance of biodiversity in evolving metacommunities, using the bacteriumPseudomonas fluorescensSBW25 as a laboratory model of adaptive radiation. We found that intercommunity spatial heterogeneity promoted phenotypic diversity ofP. fluorescensin the presence of dispersal among local communities, by allowing the spatial storage effect to operate. Mechanistically, greater niche differences amongP. fluorescensphenotypes arose in metacommunities with intercommunity spatial heterogeneity, facilitating negative frequency-dependent selection, and thus, the coexistence amongP. fluorescensphenotypes. These results highlight the importance of the spatial storage effect for biodiversity over evolutionary timescales.
The evolutionary history of 2,658 cancers
Authors: Gerstung Moritz , Jolly Clemency , Leshchiner Ignaty , Dentro Stefan C. , Gonzalez Santiago , Rosebrock Daniel , Mitchell Thomas J. , Rubanova Yulia , Anur Pavana , Yu Kaixian , Tarabichi Maxime , Deshwar Amit , Wintersinger Jeff , Kleinheinz Kortine , Vázquez-García Ignacio , Haase Kerstin , Jerman Lara , Sengupta Subhajit , Macintyre Geoff , Malikic Salem , Donmez Nilgun , Livitz Dimitri G. , Cmero Marek , Demeulemeester Jonas , Schumacher Steven , Fan Yu , Yao Xiaotong , Lee Juhee , Schlesner Matthias , Boutros Paul C. , Bowtell David D. , Zhu Hongtu , Getz Gad , Imielinski Marcin , Beroukhim Rameen , Sahinalp S. Cenk , Ji Yuan , Peifer Martin , Markowetz Florian , Mustonen Ville , Yuan Ke , Wang Wenyi , Morris Quaid D. , Spellman Paul T. , Wedge David C. , Loo Peter Van ,   on behalf of the PCAWG Evolution and Heterogeneity Working Group,   the PCAWG network
Published: July 2017

Cancer develops through a process of somatic evolution. Here, we use whole-genome sequencing of 2,778 tumour samples from 2,658 donors to reconstruct the life history, evolution of mutational processes, and driver mutation sequences of 39 cancer types. The early phases of oncogenesis are driven by point mutations in a small set of driver genes, often including biallelic inactivation of tumour suppressors. Early oncogenesis is also characterised by specific copy number gains, such as trisomy 7 in glioblastoma or isochromosome 17q in medulloblastoma. By contrast, increased genomic instability, a nearly four-fold diversification of driver genes, and an acceleration of point mutation processes are features of later stages. Copy-number alterations often occur in mitotic crises leading to simultaneous gains of multiple chromosomal segments. Timing analysis suggests that driver mutations often precede diagnosis by many years, and in some cases decades, providing a window of opportunity for early cancer detection.
omniCLIP: Bayesian identification of protein-RNA interactions from CLIP-Seq data
Authors: Drewe-Boss Philipp , Wessels Hans-Hermann , Ohler Uwe
Published: July 2017

High-throughput immunoprecipitation methods to analyze RNA binding protein – RNA in-teractions and modifications have great potential to further the understanding of post-tran-scriptional gene regulation. Due to the differences between individual approaches, each of a diverse number of computational methods can typically be applied to only one specific se-quencing protocol. Here, we present a Bayesian model called omniCLIP that can be applied to data from all protocols to detect regulatory elements in RNAs. omniCLIP greatly sim-plifies the data analysis, increases the reliability of results and paves the way for integrative studies based on data from different sources.
2-Wayk-Means as a Model for Microbiome Samples
Authors: Jackson Weston J. , Agarwal Ipsita , Pe’er Itsik
Published: July 2017

Motivation

Microbiome sequencing allows defining clusters of samples with shared composition. However, this paradigm poorly accounts for samples whose composition is a mixture of cluster-characterizing ones, and therefore lie in-between them in cluster space. This paper addresses unsupervised learning of 2-way clusters. It defines a mixture model that allows 2-way cluster assignment and describes a variant of generalizedk-means for learning such a model. We demonstrate applicability to microbial 16S rDNA sequencing data from the Human Vaginal Microbiome Project.

Contact

wjj2106@columbia.edu
Detecting environment-dependent diversification from phylogenies: a simulation study and some empirical illustrations
Authors: Lewitus Eric , Morlon Hélène
Published: July 2017

Understanding the relative influence of various abiotic and biotic variables on diversification dynamics is a major goal of macroevolutionary studies. Recently, phylogenetic approaches have been developed that make it possible to estimate the role of various environmental variables on diversification using time-calibrated species trees, paleoenvironmental data, and maximum-likelihood techniques. These approaches have been effectively employed to estimate how speciation and extinction rates vary with key abiotic variables, such as temperature and sea level, and we can anticipate that they will be increasingly used in the future. Here we compile a series of biotic and abiotic paleodatasets that can be used as explanatory variables in these models and use simulations to assess the statistical properties of the approach when applied to these paleodatasets. We demonstrate that environment-dependent models perform well in recovering environment-dependent speciation and extinction parameters, as well as in correctly identifying the simulated environmental model when speciation isenvironment-dependent. We explore how the strength of the environment-dependency, tree size, missing taxa, and characteristics of the paleoenvironmental curves influence the performance of the models. Finally, using these models, we infer environment-dependent diversification in three empirical phylogenies: temperature-dependence in Cetacea,δ13C-dependence in Ruminantia, andCO2-dependence in Portulacaceae. We illustrate how to evaluate the relative importance of abiotic and biotic variables in these three clades and interpret these results in light of macroevolutionary hypotheses for mammals and plants. Given the important role paleoenvironments are presumed to have played in species evolution, our statistical assessment of how environment-dependent models behave is crucial for their utility in macroevolutionary analysis.
GIGYF1/2 proteins use auxiliary sequences to selectively bind to 4EHP and repress target mRNA expression
Authors: Peter Daniel , Weber Ramona , Sandmeir Felix , Wohlbold Lara , Helms Sigrun , Bawankar Praveen , Valkov Eugene , Igreja Cátia , Izaurralde Elisa
Published: July 2017

The eIF4E homologous protein (4EHP) is thought to repress translation by competing with eIF4E for binding to the 5′ cap structure of specific mRNAs to which it is recruited through interactions with various proteins, including the GRB10-interacting GYF (glycine–tyrosine–phenylalanine domain) proteins 1 and 2 (GIGYF1/2). Despite its similarity to eIF4E, 4EHP does not interact with eIF4G and therefore fails to initiate translation. In contrast to eIF4G, GIGYF1/2 bind selectively to 4EHP but not eIF4E. Here, we present crystal structures of the 4EHP-binding regions of GIGYF1 and GIGYF2 in complex with 4EHP, which reveal the molecular basis for the selectivity of the GIGYF1/2 proteins for 4EHP. Complementation assays in a GIGYF1/2-null cell line using structure-based mutants indicate that 4EHP requires interactions with GIGYF1/2 to down-regulate target mRNA expression. Our studies provide structural insights into the assembly of 4EHP–GIGYF1/2 repressor complexes and reveal that rather than merely facilitating 4EHP recruitment to transcripts, GIGYF1/2 proteins are required for repressive activity.
Disrupted prenatal RNA processing and myogenesis in congenital myotonic dystrophy
Authors: Thomas James D. , Sznajder Łukasz J. , Bardhi Olgert , Aslam Faaiq N. , Anastasiadis Zacharias P. , Scotti Marina M. , Nishino Ichizo , Nakamori Masayuki , Wang Eric T. , Swanson Maurice S.
Published: July 2017

Myotonic dystrophy type 1 (DM1) is a CTG microsatellite expansion (CTGexp) disorder caused by expression of CUGexp RNAs. These mutant RNAs alter the activities of RNA processing factors, including MBNL proteins, leading to re-expression of fetal isoforms in adult tissues and DM1 pathology. While this pathogenesis model accounts for adult-onset disease, the molecular basis of congenital DM (CDM) is unknown. Here, we test the hypothesis that disruption of developmentally regulated RNA alternative processing pathways contributes to CDM disease. We identify prominent alternative splicing and polyadenylation abnormalities in infant CDM muscle, and, although most are also misregulated in adult-onset DM1, dysregulation is significantly more severe in CDM. Furthermore, analysis of alternative splicing during human myogenesis reveals that CDM-relevant exons undergo prenatal RNA isoform transitions and are predicted to be disrupted by CUGexp-associated mechanisms in utero. To test this possibility and the contribution of MBNLs to CDM pathogenesis, we generated mouse Mbnl double (Mbnl1; Mbnl2) and triple (Mbnl1; Mbnl2; Mbnl3) muscle-specific knockout models that recapitulate the congenital myopathy, gene expression, and spliceopathy defects characteristic of CDM. This study demonstrates that RNA misprocessing is a major pathogenic factor in CDM and provides novel mouse models to further examine roles for cotranscriptional/post-transcriptional gene regulation during development.
Crystal structure of 2-chloro-5-(3-hydroxy-3-methylbut-1-yn-1-yl)pyrimidine
Authors: Hübscher Jörg , Seichter Wilhelm , Weber Edwin
Published: July 2017

In the title compound, C9H9ClN2O, the ethynylpyrimidine moiety displays an almost planar geometry. In the crystal, molecules are linked by O—H...N and C—Hpyrimidine...O hydrogen bonds, forming a three-dimensional supramolecular architecture.
cis-Chloridobis(4,4′-dimethyl-2,2′-bipyridine)nitrosylruthenium(II) bis(hexafluorophosphate)
Authors: Mohammed Hasan Shamran , Tassé Marine , Malfant Isabelle , Vendier Laure
Published: July 2017

In the cation of the title complex, [RuCl(NO)(C12H12N2)2](PF6)2, the central RuII ion is sixfold coordinated by a chloride ion and a nitrosyl ligand, which are cis to one another, and by four N atoms of two 4,4′-dimethyl-2,2′-bipyridine ligands, in a slightly distorted octahedral geometry. One of the PF6
− anions is located in a general position, while the other is composed of two half PF6
− anions located on twofold rotation axes. The crystal packing is dominated by C—H...F hydrogen bonds, leading to the formation of a three-dimensional supramolecular structure. There are also C—H...Cl hydrogen bonds present.
1,4-Dihexyl-1,2,3,4-tetrahydroquinoxaline-2,3-dione
Authors: El Bourakadi Khadija , El Bakri Youness , Sebhaoui Jihad , Rayni Ibtissam , Essassi El Mokhtar , Mague Joel T.
Published: July 2017

The title compound, C20H30N2O2, has crystallographically imposed C
2 symmetry; the hexyl side chain adopts a tttg (t = trans and g = gauche) conformation. In the crystal, C—H...O hydrogen bonds link the molecules into chains extending along the b-axis direction. These chains pack to form zigzag sheets lying parallel to (101).
2-Sulfanylidene-1,3-dithiolo[4,5-b]pyrazine-5,6-dicarbonitrile
Authors: Tomura Masaaki
Published: July 2017

In the title compound, C7N4S3, the molecular entity consisting of a 1,3-dithiole-2-thione with a fused pyrazine ring is planar, with an r.m.s. deviation of 0.042 (3) Å from the least-squares plane. In the crystal, molecules are linked via short intermolecular S...N contacts [3.251 (4) and 3.308 (3) Å] between the S atom of the thiocarbonyl group and N atoms of the cyano groups.
Commercial extra virgin olive oils
Authors: Giansante Lucia , Di Loreto Giuseppina , Di Serio Maria Gabriella , Vito Raffaella , Di Giacinto Luciana
Published: July 2017

Purpose

The purpose of this paper is to guide the choice of consumers, putting on the label an additional claim, which can provide more information on the sensory profile and the nutritional and preservation features of the marketed extra virgin olive oil.

Design/methodology/approach

In order to define the concept of global quality, the following parameters were considered: fruity, bitter, pungency, 1-penten-3-one, phenolic substances, tocopherols, peroxide value, free acidity, palmitic acid, stearic acid oleic acid linoleic acid, and the campesterol/stigmasterol ratio. The study was carried out on 143 commercial extra virgin olive oils.

Findings

The Global Quality Index was calculated as the square root of the sum of the squares of the individual local indices, according to three different algorithms. The computation obtained was recognised by chemometric analysis.

Social implications

A legislative amendment on the labelling could be proposed through an additional claim that safeguards the consumers on the health profile, inducing them to a more targeted purchase.

Originality/value

Three different global quality levels “excellent”, “good”, and “sufficient” have been determined. This clustering has also been recognised with a statistical approach. Since in the market, consumers can find extra virgin olive oils of different overall quality levels, it is possible to guide the choice of customers through an additional claim on the label, able to give more information on the sensory profile and the nutritional and preservation features of the product.
Bioactive compounds by UPLC-PDA in different cocoa clones (Theobroma cacao L.) developed in the Southern region of Bahia, Brazil
Authors: Fonseca Maciel Leonardo , Felício Ana Lúcia de Souza Madureira , Hirooka Elisa Yoko
Published: July 2017

Purpose

Many factors can influence the bioactive compounds in cocoa beans. The purpose of this paper is to characterize the bioactive compound profile of 12 cocoa bean clones produced in Bahia’s Southern region.

Design/methodology/approach

Total phenolic content, total flavonoids and total anthocyanins were determined using spectrophotometric methods. Caffeic acid, caffeine, theobromine, catechin and epicatechin contents were determined using Ultra Performance Liquid Chromatography with a Photodiode Array Detector. Principal component analysis (PCA) was carried out using to determine the variability of the results found in relation to the clones studied.

Findings

The authors observed variations in the bioactive compound content between the analyzed cocoa clones. The SRN clone showed the highest levels of phenolic content, flavonoids, caffeine, catechin, and epicatechin. PCA showed that all the clones had unique characteristics related to the composition of their bioactive compounds content, classifying each clone in a well-defined manner.

Originality/value

This work is an important contribution for the characterization of new cocoa bean clones in relation to their content of bioactive compounds. The information reported in this paper can be decisive in the choice of the variety of cocoa in the production of chocolate with high bioactive compounds content and claim of functional property.
Modeling rice grain-type preferences in Bangladesh
Authors: Mottaleb Khondoker Abdul , Rahut Dil Bahadur , Mishra Ashok K.
Published: July 2017

Purpose

The purpose of this paper is to examine the rice consumption by rice grain types under the rising income scenario in Bangladesh. Generally, with an increase in income, households tend to consume more food items that are high-value, enriched foods and protein, such as meat and fish, by substituting for cereals. However, consumers also substitute when it comes to grain quality. For example, cereals, such as rice, are available in a range of qualities from the ordinary type (coarse-grain) to the premium type (fine grain). The authors postulate that as household incomes increase, households may consume more premium-type rice (or fine-grain rice), while overall consuming less rice or fewer carbohydrates.

Design/methodology/approach

Using the Bangladesh Household Income and Expenditure Survey 2000, 2005, and 2010, and applying multivariate probit and seemingly unrelated regression estimation procedures, this study quantifies the impact of income, household demographics, and urbanization on rice consumption by rice grain types (coarse-grain, medium-grain, and fine-grain types).

Findings

The results show that urban, wealthy households and, households headed by educated heads and spouses, are more likely to consume fine-grain rice than their counterparts.

Originality/value

After yield, grain type is the second most important factor for farmers when considering the adoption of a new variety. The price of rice and other cereals is highly associated with the grain type. This study concludes that plant breeding programs of major cereals, such as rice and wheat, should take into account the consumer grain-type preferences when developing new varieties.
Who is the purchaser of nutrition-labelled products?
Authors: Smed Sinne , Edenbrandt Anna Kristina , Koch-Hansen Pia , Jansen Leon
Published: July 2017

Purpose

The purpose of this paper is to determine how the typical purchasers of products with nutrition symbols differ from other purchasers with respect to socio-demographic characteristics. Furthermore the authors examine if the typical purchaser is similar across six product types in Denmark and in the Netherlands.

Design/methodology/approach

The authors estimate probit models using a representative panel of households registering all their daily purchases during a year, three years after the introduction of a nutrition symbol in Denmark and the Netherlands (the Keyhole and the Choices). The purchase data are matched with information about labelling status. Other product and purchase characteristics, such as store-type and organic, are controlled for.

Findings

Households with children tend to have a lower probability of purchasing labelled products compared to other household types, while urbanity increases the probability. This holds both across countries and across products. In Denmark education is positively correlated with label purchase, while in the Netherlands it is income. Generally, the observable characteristics of the consumers are poor in explaining the probability of purchasing labelled products which suggests that other aspects as the underlying attitudes and general health awareness may be of greater importance in identifying these consumers.

Originality/value

There is a lack of studies analysing the effect of front-of-pack symbols on households’ product choices based on observed data as most previous studies are based on stated observation or purchase intentions.
Opt-in or opt-out: exploring how women construe their ambition at early career stages
Authors: Harman Charlotte , Sealy Ruth
Published: July 2017

Purpose

The purpose of this paper is to challenge existing models of career ambition, extending understanding of how women define and experience ambition at early career stages in a professional services organisation.

Design/methodology/approach

Semi-structured interviews were conducted with 20 women from a professional services organisation, who were aged 24-33 and had not yet reached managerial positions. The interviews were recorded, transcribed and template analysis was conducted.

Findings

The analysis revealed four main themes in the women’s experiences: subjective, dynamic ambition; frustrated lack of sight; self-efficacy enables ambition; and a need for resilience vs a need to adapt. The findings support that women do identify as ambitious, but they vary in the extent to which they view ambition as intrinsic and stable, or affected by external, contextual factors, such as identity-fit, barriers, support and work-life conflict.

Research limitations/implications

These results demonstrated insufficiency of current models of ambition and a new model was proposed. The model explains how women’s workplace experiences affect their ambition and therefore how organisations and individuals can better support women to maintain and fulfil their ambitions.

Originality/value

This study extends and contributes to the redefinition of women’s career ambition, proposing a model incorporating women’s affective responses to both internal (psychological) and external (organisational) factors. It provides further evidence against previous individual-level claims that women “opt-out” of their careers due to an inherent lack of ambition, focussing on the interplay of contextual-level explanations.
Organizational structure and innovation performance
Authors: Dedahanov Alisher Tohirovich , Rhee Changjoon , Yoon Junghyun
Published: July 2017

Purpose

The purpose of this paper is to investigate the mediating role of innovative behavior on the relationships between organizational structure, such as centralization, formalization, integration, and organizational innovation performance.

Design/methodology/approach

The authors collected data from 140 functional managers of manufacturing organizations in the Republic of Korea. The authors used structural equation modeling procedure to evaluate the validity of proposed hypotheses.

Findings

The results suggest that innovative behavior mediates the links among centralization, formalization, and organizational innovation performance. However, the findings indicate that innovative behavior does not mediate the relationship between integration and organizational innovation performance.

Originality/value

This work is the first to examine the mediating role of innovative behavior on the associations among centralization, integration, and organizational innovation performance.