bluuebunny/crossref_metadata_2025 huggingface dataset:
Sleep Medications Containing Melatonin can Potentially Induce Ventricular Arrhythmias in Structurally Normal Hearts: A 2-Patient Report
Authors: de Vries Lennart J. , Géczy Tamas , Szili-Torok Tamas
Published: July 2017

Idiopathic ventricular arrhythmias (IVAs) are relatively common in the general population and usually have a good prognosis. However, frequent premature ventricular contractions (PVCs) can lower the quality of life (in symptomatic cases) and can cause cardiomyopathy and sudden cardiac death. In this report, we demonstrate a novel trigger for IVAs. Melatonin use for treating sleep disorders has increased significantly in recent years. We provide here the first human evidence of its proarrhythmic effect by presenting 2 patients (with normal myocardium) with symptomatic PVCs, while on melatonin. Discontinuation of melatonin stopped PVCs in both patients. Our findings highlight the importance of identifying precipitating factors for IVAs.
Genetics Influence Neurocognitive Performance at Baseline but Not Concussion History in Collegiate Student-Athletes
Authors: Cochrane Graham D. , Sundman Mark H. , Hall Eric E. , Kostek Matthew C. , Patel Kirtida , Barnes Kenneth P. , Ketcham Caroline J.
Published: July 2017

Objective:

This study investigates 4 single-nucleotide polymorphisms [Apolipoprotein E (APOE), APOE promoter, catechol-O-methyl transferase (COMT), and dopamine D2 receptor] that have been implicated in concussion susceptibility and/or cognitive ability in collegiate student-athletes.

Design:

Cross-sectional study.

Setting:

Neuroscience laboratory at Elon University.

Participants:

Two hundred fifty division I collegiate student-athletes (66 women, 184 men) from various sports.

Intervention:

All participants completed Immediate Postconcussion Assessment and Cognitive Testing (ImPACT) testing at baseline concussion testing and had a buccal swab taken for DNA for genotyping.

Main Outcome Measures:

Self-reported history of concussions and neurocognitive performance were taken from ImPACT.

Results:

Individuals carrying an ε4 allele in their APOE gene had a significantly slower reaction time (P = 0.001). Individuals homozygous for the Val allele of the COMT gene showed significantly worse impulse control scores (P = 0.014). None of the genotypes were able to predict self-reported concussion history in collegiate student-athletes.

Conclusions:

These results indicate that certain genotypes may influence performance on cognitive testing at baseline and that the APOE genotypes may not influence concussion susceptibility as suggested by past studies.
Significance of Endolymphatic Hydrops in Ears With Unilateral Sensorineural Hearing Loss
Authors: Okazaki Yuriko , Yoshida Tadao , Sugimoto Satofumi , Teranishi Masaaki , Kato Ken , Naganawa Shinji , Sone Michihiko
Published: July 2017

Objective:

The purpose of this study was to investigate the existence of endolymphatic hydrops (EH) in affected and unaffected ears in patients with unilateral sensorineural hearing loss (SNHL) using contrast-enhanced magnetic resonance imaging (MRI), and to evaluate the significance of EH in various otological diseases.

Study Design:

Retrospective study.

Setting:

University hospital.

Methods:

One hundred eighty-two ears from 91 patients with unilateral SNHL were studied. The endolymphatic space was evaluated using 3-Tesla MRI with gadodiamide hydrate. Imaging data about the degree of EH in the cochlea and vestibule were analyzed and compared between ears with various otological diseases.

Results:

All affected ears with delayed endolymphatic hydrops had EH. In affected ears with definite Menière's disease, cochlear EH was observed in all ears and vestibular EH in 93% of ears, and these rates were significantly higher in the affected than in the unaffected ears. EH was also observed in the cochlea and vestibule in 66% and 41%, respectively, of the affected ears with idiopathic sudden SNHL; however, these percentages did not differ significantly from those in the unaffected ears (52% and 38%, respectively).

Conclusion:

MRI showed that a high percentage of ears affected by Menière's disease or delayed endolymphatic hydrops had EH. Further studies should evaluate the implications of EH in ears, especially in those with sudden SNHL, in terms of secondary or pre-existing EH.
The management of pediatric hearing loss caused by auditory neuropathy spectrum disorder
Authors: Pham Nguyen S.
Published: July 2017

Purpose of review

Auditory neuropathy spectrum disorder (ANSD) is a condition in which auditory testing reveals normal otoacoustic emissions, but auditory brainstem testing is abnormal or absent and speech discrimination is poor. This constellation of findings ostensibly suggests that the cochlea is healthy and an abnormality of conduction or processing of sound occurs along the nerve fibers. As more is learned about this condition, it is becoming clear that ANSD describes heterogeneous, distinct clinical entities that must be taken into account when devising treatment modalities.

Recent findings

Modern auditory testing, genetic testing, and neuroimaging can allow for an accurate understanding of the location of the lesion causing ANSD in the auditory pathway. Contributing causes can include genetic mutations, absent or deficient cochlear nerve, hypoxia and jaundice among others. Hearing aids can be successful in the management of ANSD. Several studies suggest that cochlear implantation can lead to successful hearing outcomes in a subset of this patient population.

Auditory neuropathy spectrum disorder represents a relatively rare but important diagnosis for clinicians. Treatment for this condition includes hearing aids and FM systems in more mild cases, and cochlear implants in severe cases. Cochlear implantation for many patients can lead to a good hearing outcomes but the outcome can vary greatly depending on the underlying etiology of ANSD.
The amount of nitrogen used for photosynthesis governs molecular evolution in plants
Authors: Kelly Steven
Published: July 2017

Background

Genome and transcript sequences are composed of long strings of nucleotide monomers (A, C, G and T/U) that require different quantities of nitrogen atoms for biosynthesis.

Results

Here it is shown that the strength of selection acting on transcript nitrogen content is determined by the amount of nitrogen plants require to conduct photosynthesis. Specifically, plants that require more nitrogen to conduct photosynthesis experience stronger selection on transcript sequences to use synonymous codons that cost less nitrogen to biosynthesise. It is further shown that the strength of selection acting on transcript nitrogen cost constrains molecular sequence evolution such that genes experiencing stronger selection evolve at a slower rate.

Conclusions

Together these findings reveal that the plant molecular clock is set by photosynthetic efficiency, and provide a mechanistic explanation for changes in plant speciation rates that occur concomitant with improvements in photosynthetic efficiency and changes in the environment such as light, temperature, and atmospheric CO2concentration.
Anterolateral entorhinal-hippocampal imbalance in older adults disrupts object pattern separation
Authors: Reagh Zachariah M. , Noche Jessica A. , Tustison Nicholas J. , Delisle Derek , Murray Elizabeth A. , Yassa Michael A.
Published: July 2017

The entorhinal cortex (EC) is among the earliest brain areas to deteriorate in Alzheimer’s disease (AD). However, the extent to which functional properties of the EC are altered in the aging brain, even in the absence of clinical symptoms, is not understood. Recent human fMRI studies have identified a functional dissociation within the EC, similar to what is found in rodents. Here, we used high-resolution fMRI to identify a specific hypoactivity in the anterolateral EC (alEC) commensurate with major behavioral deficits on an object pattern separation task in asymptomatic older adults. Only subtle deficits were found in a comparable spatial condition, with no associated differences in posteromedial EC between young and older adults. We additionally link this condition to previously reported dentate/CA3 hyperactivity, both of which were associated with object mnemonic discrimination impairment. These results provide novel evidence of alEC-dentate/CA3 circuit dysfunction in cognitively normal aged humans.
A Radically New Theory of how the Brain Represents and Computes with Probabilities
Authors: Rinkus Gerard (Rod)
Published: July 2017

Many believe that the brain implements probabilistic reasoning and that it represents information via some form of population (distributed) code. Most prior probabilistic population coding (PPC) theories share basic properties: 1) continuous-valued units; 2) fully/densely distributed codes; 3) graded synap-ses; 4) rate coding; 5) units have innate low-complexity, usually unimodal, tuning functions (TFs); and 6) units are intrinsically noisy and noise is generally considered harmful. I describe a radically different theory that assumes: 1) binary units; 2) sparse distributed codes (SDC); 3)functionallybinary synapses; 4) a novel,atemporal, combinatorial spike code; 5) units initially have flat TFs (all weights zero); and 6) noise is a resource generated/used, normatively, to cause similar inputs to map to similar codes. The theory, Sparsey, was introduced 25+ years ago as: a) an explanation of the physical/computational relationship of episodic and semantic memory for the spatiotemporal (sequential) pattern domain; and b) a canonical, mesoscale cortical probabilistic circuit/algorithm possessing fixed-time, unsupervised, single-trial, non-optimization-based, unsupervised learning and fixed-time best-match (approximate) retrieval; but was not described as an alternative to PPC-type theories. Here, we show that: a) the active SDC in a Sparsey coding field (CF) simultaneously represents not only the likelihood of the single most likely input but the likelihoods of all hypotheses stored in the CF; and b) the whole explicit distribution can be sent, e.g., to a downstream CF, via a set of simultaneous single spikes from the neurons comprising the active SDC.
A comprehensive map of genetic variation in the world’s largest ethnic group - Han Chinese
Authors: Chiang Charleston W. K. , Mangul Serghei , Robles Christopher R. , Kretzschmar Warren W. , Cai Na , Kendler Kenneth S. , Sankararam Sriram , Flint Jonathan
Published: July 2017

As are most non-European populations around the globe, the Han Chinese are relatively understudied in population and medical genetics studies. From low-coverage whole-genome sequencing of 11,670 Han Chinese women we present a catalog of 25,057,223 variants, including 548,401 novel variants that are seen at least 10 times in our dataset. Individuals from our study come from 19 out of 22 provinces across China, allowing us to study population structure, genetic ancestry, and local adaptation in Han Chinese. We identify previously unrecognized population structure along the East-West axis of China and report unique signals of admixture across geographical space, such as European influences among the Northwestern provinces of China. Finally, we identified a number of highly differentiated loci, indicative of local adaptation in the Han Chinese. In particular, we detected extreme differentiation among the Han Chinese at MTHFR, ADH7, and FADS loci, suggesting that these loci may not be specifically selected in Tibetan and Inuit populations as previously suggested. On the other hand, we find that Neandertal ancestry does not vary significantly across the provinces, consistent with admixture prior to the dispersal of modern Han Chinese. Furthermore, contrary to a previous report, Neandertal ancestry does not explain a significant amount of heritability in depression. Our findings provide the largest genetic data set so far made available for Han Chinese and provide insights into the history and population structure of the world’s largest ethnic group.
The Detection of Phase Amplitude Coupling During Sensory Processing
Authors: Seymour R.A , Rippon G. , Kessler K.
Published: July 2017

1.

There is increasing interest in understanding how the phase and amplitude of distinct neural oscillations might interact to support dynamic communication within the brain. In particular, previous work has demonstrated a coupling between the phase of low frequency oscillations and the amplitude (or power) of high frequency oscillations during certain tasks, termed phase amplitude coupling (PAC). For instance, during visual processing in humans, PAC has been reliably observed between ongoing alpha (8-13Hz) and gamma-band (>40Hz) activity. However, the application of PAC metrics to electrophysiological data can be challenging due to numerous methodological issues and lack of coherent approaches within the field. Therefore, in this article we outline the various analysis steps involved in detecting PAC, using an openly available MEG dataset from 16 participants performing an interactive visual task. Firstly, we localised gamma and alpha-band power using the Fieldtrip toolbox, and extracted time courses from area V1, defined using a multimodal parcellation scheme. These V1 responses were analysed for changes in alpha-gamma PAC, using four common algorithms. Results showed an increase in gamma (40-100Hz) - alpha (7-13Hz) PAC in response to the visual grating stimulus, though specific patterns of coupling were somewhat dependent upon the algorithm employed. Additionally, post-hoc analyses showed that these results were not driven by the presence of non-sinusoidal oscillations, and that trial length was sufficient to obtain reliable PAC estimates. Finally, throughout the article, methodological issues and practical guidelines for ongoing PAC research will be discussed.
Phylogenomics of the olive tree (Olea europaea) disentangles ancient allo- and autopolyploidizations in Lamiales
Authors: Julca Irene , Marcet-Houben Marina , Vargas Pablo , Gabaldón Toni
Published: July 2017

Background

Polyploidization is one of the major evolutionary processes that shape eukaryotic genomes, being particularly common in plants. Polyploids can arise through direct genome doubling within a species (autopolyploidization) or through the merging of genomes from distinct species after hybridization (allopolyploidization). The relative contribution of either mechanism in plant evolution is debated. Here we used phylogenomics to dissect the tempo and mode of duplications in the genome of the olive tree (Olea europaea), one of the first domesticated Mediterranean fruit trees.

Results

Our results depict a complex scenario involving at least three past polyploidization events, of which two -at the bases of the family Oleaceae and the tribe Oleeae, respectively- are likely to be the result of ancient allopolyploidization. A more recent polyploidization involves specifically the olive tree and relatives.

Conclusion

Our results show the power of phylogenomics to distinguish between allo- and auto- polyplodization events and clarify the conundrum of past duplications in the olive tree lineage.
Resequencing theEscherichia coligenome by GenoCare single molecule sequencing platform
Authors: Zhao Luyang , Deng Liwei , Li Gailing , Jin Huan , Cai Jinsen , Shang Huan , Li Yan , Yang Andrew X. , Chen Fang , Zhao Zhi , Xu Guanjie , Liu Wuxing , Liu Siyu , Xiang Guobing , Liu Bin , Xu Weibin , Zeng Lidong , Zhang Renli , Zhao Huan , Wu Ping , Zhou Zhiliang , Zheng Jiao , Ezanno Pierre , Chen Weiyue , Yan Qin , Deem Michael W. , Yu Jun , He Jiankui
Published: July 2017

Next generation sequencing (NGS) has revolutionized life sciences research. Recently, a new class of third-generation sequencing platforms has arrived to meet increasing demands in the clinic, capable of directly measuring DNA and RNA sequences at the single-molecule level without amplification. Here, we use the new GenoCare single molecule sequencing platform from Direct Genomics to resequence theE. coligenome and show comparable performance to the Illumina MiSeq system. Our platform detects single-molecule fluorescence by total internal reflection microscopy, with sequencing-by-synthesis chemistry. With a consensus sequence of 99.71% nucleotide identity to that of the Illumina MiSeq system’s, GenoCare was determined to be a reliable platform for single-molecule sequencing, with strong potential for clinical applications.
Wide sampling of natural diversity identifies novel molecular signatures of C4photosynthesis
Authors: Kelly Steven , Covshoff Sarah , Wanchana Samart , Thakur Vivek , Quick W. Paul , Wang Yu , Ludwig Martha , Bruskiewich Richard , Fernie Alisdair R. , Sage Rowan F. , Tian Zhijian , Yan Zixian , Wang Jun , Zhang Yong , Zhu Xin-Guang , Ka-Shu Wong Gane , Hibberd Julian M.
Published: July 2017

Introductory paragraph

Much of biology is associated with convergent traits, and it is challenging to determine the extent to which underlying molecular mechanisms are shared across phylogeny. By analyzing plants representing eighteen independent origins of C4photosynthesis, we quantified the extent to which this convergent trait utilises identical molecular mechanisms. We demonstrate that biochemical changes that characterise C4species are recovered by this process, and expand the paradigm by four metabolic pathways not previously associated with C4photosynthesis. Furthermore, we show that expression of many genes that distinguish C3and C4species respond to low CO2, providing molecular evidence that reduction in atmospheric CO2was a driver for C4evolution. Thus the origin and architecture of complex traits can be derived from transcriptome comparisons across natural diversity.
TriPoly: a haplotype estimation approach for polyploids using sequencing data of related individuals
Authors: Motazedi Ehsan , Ridder Dick de , Finkers Richard , Maliepaard Chris
Published: July 2017

Knowledge of “haplotypes”, i.e. phased and ordered marker alleles on a chromosome, is essential to answer many questions in genetics and genomics. By generating short pieces of DNA sequence, high-throughput modern sequencing technologies make estimation of haplotypes possible for single individuals. In polyploids, however, haplotype estimation methods usually require deep coverage to achieve sufficient accuracy. This often renders sequencing-based approaches too costly to be applied to large populations needed in studies of Quantitative Trait Loci (QTL).

We propose a novel haplotype estimation method for polyploids, TriPoly, that combines sequencing data with Mendelian inheritance rules to infer haplotypes in parent-offspring trios. Using realistic simulations of short- read sequencing data for potato (Solanum tuberosum) and banana (Musa acuminata) trios, we show that TriPoly yields more accurate progeny haplotypes at low coverages compared to the existing methods that work on single individuals.
Qinichelins, novel catecholate-hydroxamate siderophores synthesized via a multiplexed convergent biosynthesis pathway
Authors: Gubbens Jacob , Wu Changsheng , Zhu Hua , Filippov Dmitri V. , Florea Bogdan I. , Rigali Sébastien , Overkleeft Herman S. , van Wezel Gilles P.
Published: July 2017

The explosive increase in genome sequencing and the advances in bioinformatic tools have revolutionized the rationale for natural product discovery from actinomycetes. In particular, this has revealed that actinomycete genomes contain numerous orphan gene clusters that have the potential to specify many yet unknown bioactive specialized metabolites, representing a huge unexploited pool of chemical diversity. Here, we describe the discovery of a novel group of catecholate-hydroxamate siderophores termed qinichelins (2–5) fromStreptomycessp. MBT76. Correlation between the metabolite levels and the protein expression profiles identified the biosynthetic gene cluster (BGC; namedqch) most likely responsible for qinichelin biosynthesis. The structure of the molecules was elucidated by bioinformatics, mass spectrometry and NMR. Synthesis of the qinichelins requires the interplay between four gene clusters, for its synthesis and for precursor supply. This biosynthetic complexity provides new insights into the challenges scientists face when applying synthetic biology approaches for natural product discovery.

Pride repository reviewer account details:

URL:https://www.ebi.ac.uk/pride/archive/login

Project accession: PXD006577

Username: reviewer35793@ebi.ac.uk

Password: 3H0iM1FK
Immature HIV-1 Lattice Assembly Dynamics are Regulated by Scaffolding from Nucleic Acid and the Plasma Membrane
Authors: Pak Alexander J. , Grime John M. A. , Sengupta Prabuddha , Chen Antony K. , Durumeric Aleksander E. P. , Srivastava Anand , Yeager Mark , Briggs John A. G. , Lippincott-Schwartz Jennifer , Voth Gregory A.
Published: July 2017

The packaging and budding of Gag polyprotein and viral ribonucleic acid (RNA) is a critical step in the human immunodeficiency virus-1 (HIV-1) lifecycle. High-resolution structures of the Gag polyprotein have revealed that the capsid (CA) and spacer peptide 1 (SP1) domains contain important interfaces for Gag self-assembly. However, the molecular details of the multimerization process, especially in the presence of RNA and the cell membrane, have remained unclear. In this work, we investigate the mechanisms that work in concert between the polyproteins, RNA, and membrane to promote immature lattice growth. We develop a coarse-grained (CG) computational model that is derived from sub-nanometer resolution structural data. Our simulations recapitulate contiguous and hexameric lattice assembly driven only by weak anisotropic attractions at the helical CA-SP1 junction. Importantly, analysis from CG and single-particle tracking photoactivated localization (spt-PALM) trajectories indicates that viral RNA and the membrane are critical constituents that actively promote Gag multimerization through scaffolding, while over-expression of short competitor RNA can suppress assembly. We also find that the CA amino-terminal domain imparts intrinsic curvature to the Gag lattice. As a consequence, immature lattice growth appears to be coupled to the dynamics of spontaneous membrane deformation. Our findings elucidate a simple network of interactions that regulate the early stages of HIV-1 assembly and budding.

SIGNIFICANCE STATEMENT

In order for human immunodeficiency virus to proliferate, viral proteins and genomic dimers are assembled at host cell membranes and released as immature virions. Disrupting this key intermediate step in viral replication is a potential target for treatment. However, a detailed molecular view of this process remains lacking. Here, we elucidate a network of constitutive interactions that regulate viral assembly dynamics through a combined computational and experimental approach. Specifically, our analysis reveals the active roles of nucleic acid and the membrane as scaffolds that promote the multimerization of Gag polyprotein which proceeds through multi-step and self-correcting nucleation. Our findings also illustrate the functional importance of the N-terminal, C-terminal, and spacer peptide 1 protein domains.
Glycan Clock Forecasts Human Influenza A Virus Hemagglutinin Evolution
Authors: Altman Meghan O. , Angel Matthew , Košík Ivan , Trovão Nídia S. , Zost Seth J. , Gibbs James S. , Hensley Scott E. , Nelson Martha I. , Yewdell Jonathan W.
Published: July 2017

Adaptive immunity to influenza A virus is limited by frequent mutations in the immunodominant head of hemagglutinin (HA). Over the last century, the upward trend in HA-head glycosylation indicates glycan addition can increase fitness, but its role in viral evolution remains unclear. Here, we report glycan evolution follows a clock-like rhythm, pacing the timeline, trajectory, and replacement of HA. Following pandemic introduction, glycans are added to HA at 4- to 6-year intervals, until a functional glycan limit is reached, after which, at 9- to 12-year intervals, glycans are either swapped between different sites, or the HA is replaced by a novel pandemic virus. Using this, we predicted the appearance of the newest glycan on pH1N1 HA. Phylogeographic reconstruction suggests these highly fit strains originated in the Middle East, before rapidly replacing all strains globally. Going forward, we can use this simple algorithm to forecast future glycan evolution and identify seasons with higher pandemic potential.
Asleep at the Wheel: Forward Genetic ENU Mutagenesis Screen for Mouse Models of Chronic Fatigue Identifies a Mutation inSlc2a4(GLUT4)
Authors: de Groot Marleen H. M. , Castorena Carlos M. , Kumar Vivek , Mohawk Jennifer A. , Ahmed Newaz I. , Takahashi Joseph S.
Published: July 2017

In a screen of voluntary wheel-running behavior designed to identify genetic mouse models of chronic fatigue in ENU mutagenized C57BL/6J mice, we discovered two lines that showed aberrant wheel-running patterns. These lines both stem from a single original founder identified as a low body-weight candidate in a recessive screen. Progeny from both of these lines showed the abnormal wheel-running behavior, with affected mice showing significantly lower daily activity levels than unaffected mice. They also exhibited low amplitude circadian rhythms, consisting of lower activity levels during the normal active phase, and increased levels of activity during the rest or light phase, but only a modest alteration in free-running period. Their activity is not consolidated into longer bouts, but is frequently interrupted with periods of inactivity throughout the dark phase of the light-dark (LD) cycle. As seen with the low body weight, expression of the behavioral phenotypes in offspring of strategic crosses was consistent with a recessive heritance pattern. Mapping of these phenotypic abnormalities showed linkage to a single locus on chromosome 11, and whole exome sequencing (WES) identified a single point mutation in theSlc2a4gene encoding the GLUT4 insulin-responsive glucose transporter. The single nucleotide change (A to T) was found in the distal end of exon 10, and results in a premature stop (Y440*). To our knowledge, this is the first time a mutation in this gene has been shown to result in extensive changes in general behavioral patterns.

SIGNIFICANCE STATEMENT

Chronic fatigue is a debilitating and devastating disorder with widespread consequences for both the patient and the persons around them, but effective treatment strategies are lacking. The identification of novel genetic mouse models of chronic fatigue may prove invaluable for the study of its underlying physiological mechanisms and for the testing of treatments and interventions. A novel mutation inSlc2a4(GLUT4) was identified in a forward mutagenesis screen because affected mice showed abnormal daily patterns and levels of wheel running consistent with chronic fatigue. This new mouse model may shed light on the pathophysiology of chronic fatigue.
Heterogeneous Responses of Hematopoietic Stem Cells to Inflammatory Stimuli are Altered with Age
Authors: Mann Mati , Mehta Arnav , de Boer Carl , Kowalczyk Monika S. , Lee Kevin , Rogel Noga , Knecht Abigail R. , Farouq Daneyal , Regev Aviv , Baltimore David
Published: July 2017

Long-term hematopoietic stem cells (LT-HSCs) maintain hematopoietic output throughout an animal's lifespan. With age, however, they produce a myeloid-biased output that may lead to poor immune responses to infectious challenge and the development of myeloid leukemias. Here, we show that young and aged LT-HSCs respond differently to inflammatory stress, such that aged LT-HSCs produce a cell-intrinsic, myeloid-biased expression program. Using single-cell RNA-seq, we identify a myeloid-biased subset within the LT-HSC population (mLT-HSCs) that is much more common amongst aged LT-HSCs and is uniquely primed to respond to acute inflammatory challenge. We predict several transcription factors to regulate differentially expressed genes between mLT-HSCs and other LT-HSC subsets. Among these, we show thatKlf5,Ikzf1andStat3play important roles in age-related inflammatory myeloid bias. These factors may regulate myeloid versus lymphoid balance with age, and can potentially mitigate the long-term deleterious effects of inflammation that lead to hematopoietic pathologies.

Highlights

LT-HSCs from young and aged mice have differential responses to acute inflammatory challenge.

HSPCs directly sense inflammatory stimuliin vitroand have a robust transcriptional response.

Aged LT-HSCs demonstrate a cell-intrinsic myeloid bias during inflammatory challenge.

Single-cell RNA-seq unmasked the existence of two subsets within the LT-HSC population that was apparent upon stimulation but not steady-state. One of the LT-HSC subsets is more prevalent in young and the other in aged mice.

Klf5,Ikzf1andStat3regulate age‐ and inflammation-related LT-HSC myeloid-bias.

One sentence summary

Murine hematopoietic stem cells display transcriptional heterogeneity that is quantitatively altered with age and leads to the age-dependent myeloid bias evident after inflammatory challenge.
Newly qualified teachers’ professional learning through practitioner enquiry
Authors: Robson Dean , Mtika Peter
Published: July 2017

Purpose

The purpose of this paper is to focus on a partnership-based mentoring model and the learning experiences of participant mentees and mentors. As part of the project, newly qualified teachers (NQTs) were supported to develop and implement a practitioner enquiry (teacher/action research) in a learning community involving two local authorities and an initial teacher education institution.

Design/methodology/approach

Qualitative data were collected from five semi-structured focus group interviews with key participant groupings to uncover perceptions and experiences of the partnership and professional learning therein. Analysis using an inductive and iterative approach pinpointed a number of emerging themes used to frame key elements of the findings.

Findings

Findings suggested that the partnership-based model promoted the professional learning and development of NQTs and their mentors in various ways. The nature and shape of the partnership had an influence on the quality of mentoring and support experienced. The community effectively supported the implementation of meaningful enquiry projects, which had clear connections to the enhancement of professional practice and pupil learning. However, specific tensions and conflicts emerged as hindrances to successful partnership-based mentoring in the specific context.

Originality/value

New insights into the role of a partnership-based mentoring scheme supporting practitioner enquiry-based learning of NQTs emerged. The local, layered community defining the partnership, and operating within the frame of a national induction scheme, was analysed. Benefits for partners were identified and specific challenges and tensions highlighted, both providing new evidence with potential to impact policy and practice. Policy developments supporting teachers to be mentors and enquiring professionals need to recognise the structural and support tensions that exist in contextual practice.
International e-commerce for fashion products: what is the relationship with performance?
Authors: Macchion Laura , Moretto Antonella Maria , Caniato Federico , Caridi Maria , Danese Pamela , Vinelli Andrea
Published: July 2017

Purpose

The purpose of this paper is to analyse whether the adoption of e-commerce improves company business, innovation and operational performance and whether sales internationalisation might moderate this relationship.

Design/methodology/approach

The research is based on a survey within the fashion industry and a multi-step linear regression model investigating the relationships between e-commerce and performance.

Findings

Results reveal that e-commerce improves innovation performance but has no significant relationship with business and operational performance. Also investigating whether the sales internationalisation might moderate the relationship between e-commerce and performance, the findings reveal that the adoption of these tools might even be negative when applied at the international level in particular by considering innovation operational practices, and the research suggests for fashion companies the necessity to develop strong markets’ knowledge and brand awareness among foreign markets and customers before investing internationally.

Originality/value

This paper offers an original analytical approach to identifying the relationships between a company’s adoption of e-commerce, performance and internationalisation within the fashion industry.
Categorising the money management behaviour of young consumers
Authors: Bamforth Jill , Geursen Gus
Published: July 2017

Purpose

Young consumers represent a significant purchasing group, but little is known about how they make money management decisions. This study aims to identify and classify different approaches to money management that may impact purchasing behaviour.

Design/methodology/approach

Data from focus groups with 40 respondents between 18 and 24 years were recruited via campus notices across three campuses in a university in Melbourne, Australia.

Findings

Based on how respondents accommodated economic, social and psychological influences in their money management approach, the authors identified three distinct approaches to money management: conservative money managers, creative money managers and entrepreneurial money managers.

Research limitations/implications

The study is based on a small sample consisting of 40 individuals in Australia.

Practical implications

Young consumers share common traits as a group but have diverse attitudes and approaches to money management. The authors identify three distinct approaches to money management based on respondents’ management of factors affecting their money management. Companies must consider these differences to effectively approach millennial consumers.

Social implications

The indebtedness of young consumers is a common concern in society. Analysis of their approaches to money management offers an opportunity for organisations to support responsible individual money usage amongst young consumers.

Originality/value

While exploratory, the current study is the first to consider how differences in money management behaviour in young generations may impact consumer decision-making.
Letter: sprue‐like enteropathy associated with angiotensin II receptor blockers other than olmesartan
Authors: Zanelli M. , Negro A. , Santi R. , Bisagni A. , Ragazzi M. , Ascani S. , De Marco L.
Published: July 2017

Linked Content

This article is linked to Zanelli and Negro et al and Marthey and Carbonnel papers. To view these articles visit https://doi.org/10.1111/apt.14176 and https://doi.org/10.1111/apt.14191.
Letter: there's something about the Neutrophil‐to‐Lymphocyte ratio (NLR)…
Authors: Forrest E. H.
Published: July 2017

Linked Content

This article is linked to Forest and Cai and Shi et al papers. To view these articles visit https://doi.org/10.1111/apt.14183 and https://doi.org/10.1111/apt.14208.
Letter: direct‐acting agent therapy and HCV‐related Child C cirrhosis
Authors: Braillon A.
Published: July 2017

Linked Content

This article is linked to Braillon paper. To view this article visit https://doi.org/10.1111/apt.14184.
Editorial: migration studies to determine risk and cause of inflammatory bowel disease
Authors: Kuenzig M. E. , Benchimol E. I.
Published: July 2017

Linked Content

This article is linked to Kuenzig and Benchimol and Dasmas and Schwarts et al papers. To view these articles visit https://doi.org/10.1111/apt.14186 and https://doi.org/10.1111/apt.14200.
Letter: sprue‐like enteropathy associated with angiotensin II receptor blockers other than olmesartan—authors'reply
Authors: Marthey L. , Carbonnel F.
Published: July 2017

Linked Content

This article is linked to Zanelli and Negro et al and Marthey and Carbonnel papers. To view these articles visit https://doi.org/10.1111/apt.14176 and https://doi.org/10.1111/apt.14191.
Editorial: changing nature of paediatric IBD—new insights from Irish data. Author's reply
Authors: Hussey S.
Published: July 2017

Linked Content

This article is linked to Wiskin and Sandhu, and Coughlan et al papers. To view these articles visit https://doi.org/10.1111/apt.14147 and https://doi.org/10.1111/apt.14070.
Editorial: liver transplantation in patients with non‐alcoholic fatty liver disease and obesity—authors’ reply
Authors: Barone M. , Viggiani M. T. , Losurdo G. , Principi M. , Leandro G. , Di Leo A.
Published: July 2017

Linked Content

This article is linked to Townsend and Newsome et al and Barone et al papers. To view these articles visit https://doi.org/10.1111/apt.14179 and https://doi.org/10.1111/apt.14195.
Systematic review with meta‐analysis: the efficacy of faecal microbiota transplantation for the treatment of recurrent and refractory Clostridium difficile infection
Authors: Quraishi M. N. , Widlak M. , Bhala N. , Moore D. , Price M. , Sharma N. , Iqbal T. H.
Published: July 2017

Background

Clostridium difficile infection (CDI) is the commonest nosocomial cause of diarrhoea. Faecal microbiota transplantation (FMT) is an approved treatment for recurrent or refractory CDI but there is uncertainty about its use.

Aim

To evaluate the efficacy of FMT in treating recurrent and refractory CDI and investigate outcomes from modes of delivery and preparation.

Methods

A systematic review and meta‐analysis was performed. MEDLINE, EMBASE, CINAHL, Cochrane Library, trial registers and conference proceedings were searched. Studies on FMT in recurrent and refractory CDI were included. The primary outcome was clinical resolution with subgroup analyses of modes of delivery and preparation. Random effects meta‐analyses were used to combine data.

Results

Thirty seven studies were included; seven randomised controlled trials and 30 case series. FMT was more effective than vancomycin (RR: 0.23 95%CI 0.07‐0.80) in resolving recurrent and refractory CDI. Clinical resolution across all studies was 92% (95%CI 89%‐94%). A significant difference was observed between lower GI and upper GI delivery of FMT 95% (95%CI 92%‐97%) vs 88% (95%CI 82%‐94%) respectively (P=.02). There was no difference between fresh and frozen FMT 92% (95%CI 89%‐95%) vs 93% (95%CI 87%‐97%) respectively (P=.84). Administering consecutive courses of FMT following failure of first FMT resulted in an incremental effect. Donor screening was consistent but variability existed in recipient preparation and volume of FMT. Serious adverse events were uncommon.

Conclusion

Faecal microbiota transplantation is an effective treatment for recurrent and refractory Clostridium difficile infection, independent of preparation and route of delivery.
Editorial: different tests for different drugs in Crohn’s disease, or different tests for different people? Authors’ reply
Authors: Ward M. G. , Irving P. M.
Published: July 2017

Linked Content

This article is linked to Seow and Panacionne and Ward and Irving papers. To view these articles visit https://doi.org/10.1111/apt.14185 and https://doi.org/10.1111/apt.14209.
Crossing boundaries of state and religious power: Reproductive mobilities in Singapore
Authors: Mariano Danicar , Yeoh Brenda S.A. , Cheng Yi'En
Published: July 2017

Singapore has one of the tightest regulations over assisted reproductive technologies (ARTs) in Asia, a consequence of Singapore's strong state, the priority it gives to reproduction, and the numerous religious groups in the country and their direct and indirect influence on the Bioethics Advisory Committee, which recommends ART regulations for the country. Together, these key actors give shape to the ‘local moral worlds’, which undergird ART governance in the country. Drawing on in‐depth interviews and data from online forums, we illustrate Singaporean fertility seekers' attempts to juggle myriad and sometimes confusing obligations to the state, society and religion in making reproductive choices. We then explore the limits and possibilities for fertility seekers to circumvent the restrictive rules and ‘moral safety valves’ set in place in their home country simply by stepping out to another jurisdiction across national borders. The paper goes on to show how the Internet communities serve as a bridgespace, propelling fertility mobilities by enabling Singaporeans to see creative possibilities in patchwork regulations. At the edges of state and religious power, fertility‐seeking subjects take advantage of liminal spaces, grey areas, or permissive regimes to gain several degrees of freedom to practise adaptive fertility strategies that may be ‘unofficial’ but ‘licit’ or ‘socially acceptable’.
Geochemical Methods for Sourcing Lava Paving Stones from the Roman Roads of Central Italy
Authors: Worthing M. , Bannister J. , Laurence R. , Bosworth L.
Published: July 2017

This paper documents the results of in situ analysis of 306 lava paving stones and 74 possible source rocks using pXRF. Data were collected from sites both in the city of Rome—on major roads beyond the city (including the Viae Flaminia, Cassia, Clodia, Praenestina and Appia)—and in the city of Ostia. Comparison of the pXRF data with lava compositional data from the geological literature allows broad identification of possible sources. The results point to quite distinctive patterns of exploitation for the city of Rome and Ostia, utilizing the Alban Hills lava flows, and the roads of the middle Tiber Valley, drawing on lava flows associated with the Vico and Sabatini volcanoes. The results show the potential of pXRF to produce data to elucidate the exploitation of lava flows for paving the Roman roads.
Lisht as a New Kingdom Glass‐Making Site with Its Own Chemical Signature
Authors: Smirniou M. , Rehren Th. , Gratuze B.
Published: July 2017

Lisht is one of a few New Kingdom sites with known glass‐working debris. Here, we present evidence for the primary production of glass at Lisht, including crucible fragments and semi‐finished glass. We also provide 12 new chemical analyses of glass from Lisht, including trace elements. We argue that the glass made at Lisht has a specific chemical signature within the broader range of Late Bronze Age glass compositions from Egypt, further underlining the former existence of primary glass production there and offering the possibility of identifying Lisht‐made glass elsewhere in Egypt and beyond.
Expansion of BCR/ABL1+ cells requires PAK2 but not PAK1
Authors: Edlinger Leo , Berger‐Becvar Angelika , Menzl Ingeborg , Hoermann Gregor , Greiner Georg , Grundschober Eva , Bago‐Horvath Zsuzsanna , Al‐Zoughbi Wael , Hoefler Gerald , Brostjan Christine , Gille Lars , Moriggl Richard , Spittler Andreas , Sexl Veronika , Hoelbl‐Kovacic Andrea
Published: July 2017

The p21‐activated kinases (PAKs) are key nodes in oncogenic signalling pathways controlling growth, survival, and motility of cancer cells. Their activity is increased in many human cancers and is associated with poor prognosis. To date, PAK deregulation has mainly been studied in solid tumours, where PAK1 and PAK4 are the main isoforms deregulated. We show that PAK1 and PAK2 are the critical isoforms in a BCR/ABL1+ haematopoietic malignancy. In suspension, leukaemic cells deficient for PAK1 and PAK2 undergo apoptosis, while the loss of either protein is well tolerated. Transfer of medium conditioned by shPAK2‐ but not shPAK1‐expressing leukaemic cells interferes with endothelial cell growth. We found that leukaemic cells produce exosomes containing PAK2. Transfer of isolated exosomes supports endothelial cell proliferation. In parallel, we found that leukaemic cells explicitly require PAK2 to grow towards an extracellular matrix. PAK2‐deficient cells fail to form colonies in methylcellulose and to induce lymphomas in vivo. PAK2 might therefore be the critical isoform in leukaemic cells by controlling tumour growth in a dual manner: vascularization via exosome‐mediated transfer to endothelial cells and remodelling of the extracellular matrix. This finding suggests that the PAK2 isoform represents a promising target for the treatment of haematological diseases.
Melatonin receptors: molecular pharmacology and signalling in the context of system bias
Authors: Cecon Erika , Oishi Atsuro , Jockers Ralf
Published: July 2017

Melatonin, N‐acetyl‐5‐methoxytryptamine, an evolutionally old molecule, is produced by the pineal gland in vertebrates, and it binds with high affinity to melatonin receptors, which are members of the GPCR family. Among the multiple effects attributed to melatonin, we will focus here on those that are dependent on the activation of the two mammalian MT1 and MT2 melatonin receptors. We briefly summarize the latest developments on synthetic melatonin receptor ligands, including multi‐target‐directed ligands, and the characterization of signalling‐biased ligands. We discuss signalling pathways activated by melatonin receptors that appear to be highly cell‐ and tissue‐dependent, emphasizing the impact of system bias on the functional outcome. Different proteins have been demonstrated to interact with melatonin receptors, and thus, we postulate that part of this system bias has its molecular basis in differences of the expression of receptor‐associated proteins including heterodimerization partners. Finally, bias at the level of the receptor, by the expression of genetic receptor variants, will be discussed to show how a modified receptor function can have an effect on the risk for common diseases like type 2 diabetes in humans.

Linked Articles

This article is part of a themed section on Recent Developments in Research of Melatonin and its Potential Therapeutic Applications. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.16/issuetoc
Playing With Ideas: Evaluating the Impact of the Ultimate Block Party, a Collective Experiential Intervention to Enrich Perceptions of Play
Authors: Grob Rachel , Schlesinger Mark , Pace Amy , Golinkoff Roberta Michnick , Hirsh‐Pasek Kathy
Published: July 2017

Parental attitudes shape play opportunities afforded to children in home, community, and school settings. This study presents evaluation of an intervention designed to enrich parent's conception of play and its relationship with socially valued skills and capacities. On the basis of data from 291 racially and ethnically diverse parents/caregivers of young children (median age between 3 and 6) attending an event in NYC, we find the intervention helped parents conceptualize play in complex ways and altered perceptions of its impact on children's current—but not future—lives. Multivariate analyses reveal the causal pathway for these changes as exposure to multiple play sites, rather than time at the event—a finding with direct implications for exposing parents to developmental science in community settings.