bluuebunny/crossref_metadata_2025 huggingface dataset:
Sexual selection drives evolution and rapid turnover of male gene expression
Authors: Harrison Peter W. , Wright Alison E. , Zimmer Fabian , Dean Rebecca , Montgomery Stephen H. , Pointer Marie A. , Mank Judith E.
Published: March 2015

Significance

Genes with different expression between males and females (sex-biased genes) show rapid rates of sequence and expression divergence in a range of taxa. These characteristics have led many to assume that sex-biased genes are the product of sexual selection and sexual conflict, but this assumption remains to be rigorously tested. Using a phylogenetically controlled analysis of birds that exhibit diverse levels of sexual selection, we show a rapid turnover in sex-biased gene expression primarily through evolution of male expression levels and that the degree of sexual selection predicts the proportion of male-biased genes but does not account for rates of coding sequence evolution. We also discuss the impact of allometry on gene expression studies, an issue rarely discussed in the literature.
Molecular coevolution of a sex pheromone and its receptor triggers reproductive isolation in
Schizosaccharomyces pombe
Authors: Seike Taisuke , Nakamura Taro , Shimoda Chikashi
Published: March 2015

Significance

Reproductive isolation is a key event leading to speciation as suggested by the observation of living populations in nature. This paper shows that novel reproductive populations of
Schizosaccharomyces pombe
, which are reproductively isolated from the WT population, can be created by genetically altering the primary structure of a mating pheromone and its receptor. Based on the biological concept of species, this reproductive group should be regarded as a new species. This is the first report, to our knowledge, of the artificial creation of a new species of any living organism in the history of evolutional research.
Regulatory vs. inflammatory cytokine T-cell responses to mutated insulin peptides in healthy and type 1 diabetic subjects
Authors: Nakayama Maki , McDaniel Kristen , Fitzgerald-Miller Lisa , Kiekhaefer Carol , Snell-Bergeon Janet K. , Davidson Howard W. , Rewers Marian , Yu Liping , Gottlieb Peter , Kappler John W. , Michels Aaron
Published: March 2015

Significance

Certain class II major histocompatibility alleles confer disease risk for type 1 diabetes (T1D). Insulin-specific and other autoantibodies often precede T1D development, but major efforts at disease prevention using insulin preparations (subcutaneous, oral, and intranasal) to induce tolerance have not been effective. Measuring insulin-specific T-cell responses from the peripheral blood has been a challenging feat but would allow for assessment of therapeutic response in these trials. In our study, we report CD4 T-cell responses to a mutated insulin B-chain peptide in new-onset and established T1D as well as control subjects dependent on HLA-DQ genotype. Our results have important implications for the application and monitoring of insulin-specific therapies to prevent diabetes onset.
Sae2 promotes DNA damage resistance by removing the Mre11–Rad50–Xrs2 complex from DNA and attenuating Rad53 signaling
Authors: Chen Huan , Donnianni Roberto A. , Handa Naofumi , Deng Sarah K. , Oh Julyun , Timashev Leonid A. , Kowalczykowski Stephen C. , Symington Lorraine S.
Published: March 2015

Significance

Chromosomal double-strand breaks (DSBs) are cytotoxic forms of DNA damage that must be accurately repaired to maintain genome integrity. The conserved Mre11–Rad50–Xrs2/NBS1 nuclease/ATPase complex plays an important role in repair by functioning as a damage sensor and by regulation of DNA end processing to ensure repair by the most appropriate mechanism. Yeast Sae2 is known to function with Mre11 to process DNA ends, but its precise role is poorly understood. Here we show that it is the failure to remove Mre11 from DNA ends, leading to persistent DNA damage signaling and cell cycle arrest, that causes sensitivity of Sae2-deficient cells to DNA damaging agents.
A multistage mathematical approach to automated clustering of high-dimensional noisy data
Authors: Friedman Alexander , Keselman Michael D. , Gibb Leif G. , Graybiel Ann M.
Published: March 2015

Significance

Organizing large, multidimensional datasets by subgrouping data as clusters is a major challenge in many fields, including neuroscience, in which the spike activity of large numbers of neurons is recorded simultaneously. We present a mathematical approach for clustering such multidimensional datasets in a relatively high-dimensional space using as a prototype datasets characterized by high background spike activity. Our method incorporates features allowing reliable clustering in the presence of such strong background activity and, to deal with large size of datasets, incorporates automated implementation of clustering. Our approach effectively identifies individual neurons in spike data recorded with multiple tetrodes, and opens the way to use this method in other domains in which clustering of complex datasets is needed.
Tryptophan-independent auxin biosynthesis contributes to early embryogenesis in
Arabidopsis
Authors: Wang Bing , Chu Jinfang , Yu Tianying , Xu Qian , Sun Xiaohong , Yuan Jia , Xiong Guosheng , Wang Guodong , Wang Yonghong , Li Jiayang
Published: March 2015

Significance

The phytohormone indole-3-acetic acid (IAA) plays a vital role in plant growth and development. IAA can be synthesized through the precursor tryptophan (Trp), known as the Trp-dependent IAA biosynthetic pathway. However, IAA may also be synthesized through a proposed Trp-independent IAA biosynthetic pathway. Although the Trp-independent IAA biosynthesis was hypothesized 20 years ago, it remains a mystery. In this paper, we provide compelling evidence that the cytosol-localized indole synthase (INS) initiates the Trp-independent IAA biosynthetic pathway and that the spatial and temporal expression of INS plays an important role in the establishment of the apical–basal pattern during early embryogenesis, demonstrating that the Trp-dependent and -independent IAA biosynthetic pathways coordinately regulate embryogenesis of higher plants.
Politeness on Facebook
Authors: Theodoropoulou Irene
Published: March 2015

Facebook forms one of the most widely used online social networks, through which people manage their communication with diverse contacts or ‘friends’, ranging from members of the family and schoolmates to work colleagues and popular cultural idols or other people, whom they admire. Hence, it can be seen as an integral part of people’s digital presence. Against this backdrop, the aim of this paper is to investigate the ways politeness is constructed in a context, in which it is not very typical to find politeness in the Western world: The reception of birthday wishes. The focus is on the (para)linguistic reception of birthday wishes on behalf of 400 native Greek users of Facebook, aged between 25–35 years old, as evidenced in the ways they respond to birthday wishes posted on their walls. By using a combination of interactional sociolinguistics, discourse-centered online ethnography and offline ethnographic interviews, I argue that native speakers of Greek do not just stick to the politic behavior found in other languages, like English, of personally thanking their friends for their birthday wishes; rather, they employ contextualization cues, such as shifts in spelling, emoticons and punctuation markers, in order to construct frames and footings of politeness by actually reciprocating the wishes they received from their friends. The value of this study lies not only in being, to my knowledge, the first description and interpretation of an important cultural phenomenon for Greeks, which is the exchange of birthday wishes, but also it contributes towards understanding politeness in online environments, such as Facebook, which in turn is used for establishment and maintenance of interpersonal relationships, hence it can lead to smooth communication.
Intergroup rudeness and the metapragmatics of its negotiation in online discussion fora
Authors: Kleinke Sonja , Bös Birte
Published: March 2015

This study investigates the communicative practices in English and German online discussion fora as exemplified by two thematically related sample threads. Combining first- and second-order approaches to (im-)politeness, the paper focuses on the question of how participants use intergroup rudeness as a means of in- and outgroup construction and examines how intergroup rudeness is metapragmatically negotiated as the discussions unfold. The results show that intergroup rudeness as well as metapragmatic comments are handled very differently in the two communities explored. Suggesting cultural preferences, there is a much higher degree of interactivity and a clear preference for negotiation at an interpersonal level in the German discussion group; its English counterpart favours negotiation at an intergroup level. Both threads provide metapragmatic evidence that the frequent use of rudeness tokens does not automatically make rudeness an accepted norm.
“Doing deference”
Authors: Haugh Michael , Chang Wei-Lin Melody , Kádár Dániel Z.
Published: March 2015

In this paper we examine a key relational practice found in interactions in online discussion boards in Mainland China and Taiwan: ‘doing deference’. In drawing attention to a relational practice that has received attention in quite different research traditions, namely, linguistic pragmatics and conversation analysis (CA), we mean to highlight the possible advantages of an approach to analysis that draws from both in analysing relational work in CMC. We claim in the course of our analysis that the participants are orienting not only to relationships but also to identities through this practice. In this way, we suggest that online discussion boards afford both meaningful interaction and relational work. We further claim that this analysis provides support for the theoretical position that while relational practices may intersect with the emergence of identities, they remain distinct analytical concerns.
Article use and criterial features in Spanish EFL writing
Authors: Díez-Bedmar María Belén
Published: March 2015

This pilot study uses a combination of frequency measures and an accuracy
measure to explore article use in the writing of Spanish learners of English as
a foreign language (EFL). Following Bickerton’s (1981) and Huebner’s (1983)
publications, the uses of the definite, indefinite and zero articles are analysed
and (error-)tagged in a learner corpus containing texts at the A2, B1 and B2
levels of the Common European Framework of Reference for Languages (CEFR).
Three criterial features, more concretely positive linguistic features, are observed
in the learner corpus at CEFR B2 level: the higher mean of correct uses of the
zero article in non-referential contexts, their effective use and selection, and
their accurate use. The chapter also analyses the patterns in the accuracy of use
order at the three CEFR levels and provides examples of article errors.
Rab8, POSH, and TAK1 regulate synaptic growth in a Drosophila model of frontotemporal dementia
Authors: West Ryan J.H. , Lu Yubing , Marie Bruno , Gao Fen-Biao , Sweeney Sean T.
Published: March 2015

Mutations in genes essential for protein homeostasis have been identified in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) patients. Why mature neurons should be particularly sensitive to such perturbations is unclear. We identified mutations in Rab8 in a genetic screen for enhancement of an FTD phenotype associated with ESCRT-III dysfunction. Examination of Rab8 mutants or motor neurons expressing a mutant ESCRT-III subunit, CHMP2BIntron5, at the Drosophila melanogaster neuromuscular junction synapse revealed synaptic overgrowth and endosomal dysfunction. Expression of Rab8 rescued overgrowth phenotypes generated by CHMP2BIntron5. In Rab8 mutant synapses, c-Jun N-terminal kinase (JNK)/activator protein-1 and TGF-β signaling were overactivated and acted synergistically to potentiate synaptic growth. We identify novel roles for endosomal JNK-scaffold POSH (Plenty-of-SH3s) and a JNK kinase kinase, TAK1, in regulating growth activation in Rab8 mutants. Our data uncover Rab8, POSH, and TAK1 as regulators of synaptic growth responses and point to recycling endosome as a key compartment for synaptic growth regulation during neurodegenerative processes.
Macrophages retain hematopoietic stem cells in the spleen via VCAM-1
Authors: Dutta Partha , Hoyer Friedrich Felix , Grigoryeva Lubov S. , Sager Hendrik B. , Leuschner Florian , Courties Gabriel , Borodovsky Anna , Novobrantseva Tatiana , Ruda Vera M. , Fitzgerald Kevin , Iwamoto Yoshiko , Wojtkiewicz Gregory , Sun Yuan , Da Silva Nicolas , Libby Peter , Anderson Daniel G. , Swirski Filip K. , Weissleder Ralph , Nahrendorf Matthias
Published: March 2015

Splenic myelopoiesis provides a steady flow of leukocytes to inflamed tissues, and leukocytosis correlates with cardiovascular mortality. Yet regulation of hematopoietic stem cell (HSC) activity in the spleen is incompletely understood. Here, we show that red pulp vascular cell adhesion molecule 1 (VCAM-1)+ macrophages are essential to extramedullary myelopoiesis because these macrophages use the adhesion molecule VCAM-1 to retain HSCs in the spleen. Nanoparticle-enabled in vivo RNAi silencing of the receptor for macrophage colony stimulation factor (M-CSFR) blocked splenic macrophage maturation, reduced splenic VCAM-1 expression and compromised splenic HSC retention. Both, depleting macrophages in CD169 iDTR mice or silencing VCAM-1 in macrophages released HSCs from the spleen. When we silenced either VCAM-1 or M-CSFR in mice with myocardial infarction or in ApoE−/− mice with atherosclerosis, nanoparticle-enabled in vivo RNAi mitigated blood leukocytosis, limited inflammation in the ischemic heart, and reduced myeloid cell numbers in atherosclerotic plaques.
Large deviation principle of Freidlin-Wentzell type for pinned diffusion processes
Authors: Inahama Yuzuru
Published: March 2015

Since T. Lyons invented rough path theory, one of its most successful applications is a new proof of Freidlin-Wentzell’s large deviation principle for diffusion processes. In this paper we extend this method to the case of pinned diffusion processes under a mild ellipticity assumption. Besides rough path theory, our main tool is quasi-sure analysis, which is a kind of potential theory in Malliavin calculus.
Bible
Authors: Campbell Gordon
Published: March 2015

Produced during the lifetime of William Shakespeare and John Donne, the King James Version (KJV) of the Bible has long been viewed as the most elegantly written and poetic of the many English translations. Now reaching its 400th anniversary, it remains one of the most frequently used Bibles in the English-speaking world, especially in America. This book offers an authoritative history of this renowned translation, ranging from the Bible's inception to the present day. The text tells the complex story of how this translation came to be commissioned, who the translators were, and how the translation was accomplished. The book does not end with the printing of that first edition, but also traces the textual history from 1611 to the establishment of the modern text by Oxford University Press in 1769, shedding light on the subsequent generations who edited and interacted with the text and bringing to life the controversies surrounding later revisions. In addition, the book examines the reception of the KJV, showing how its popularity has shifted through time and territory, ranging from adulation to deprecation and attracting the attention of a wide variety of adherents. Since the KJV is more widely read in America today than in any other country, the book pays particular attention to the history of the KJV in the United States. Finally, the volume includes appendices that contain short biographies of the translators and a guide to the 74-page preliminaries of the 1611 edition.
Introduction
Authors: Campbell Gordon
Published: March 2015

This book chronicles the history of the King James Version (KJV) of the Bible from 1611 to 2011. Known in the United Kingdom as the Authorised Version, the KJV is the most celebrated book in the English-speaking world, particularly the United States. The book tells the complex story of how this translation came to be commissioned and accomplished, as well as the people behind the translation. Aside from its printing history, it traces the KJV's political, ecclesiastical, and cultural history from 1611 to Oxford University Press's publication of the modern version in 1769, along with the subsequent generations who edited and interacted with the text and the controversies surrounding later revisions. The reception of the King James Version is considered as well.
The Translation
Authors: Campbell Gordon
Published: March 2015

This chapter focuses on the translation of the King James Version (KJV) of the Bible. It begins with an account of the revision of the Bishops' Bible, followed by a discussion of the textual and critical apparatus used in the translation of the KJV. It then considers the language, style, and theology of the KJV.
The Eighteenth Century
Authors: Campbell Gordon
Published: March 2015

This chapter focuses on editions of the King James Version (KJV) of the Bible that were published in the eighteenth century. It first looks at the editions published by John Baskett at Oxford University Press before turning to the editions published by John Baskerville and F. S. Parris at Cambridge University Press. It then considers Benjamin Blayney's edition and concludes by assessing the reception of the KJV in the eighteenth century.
The Revised Version
Authors: Campbell Gordon
Published: March 2015

This chapter focuses on the revised edition of the King James Version (KJV) of the Bible. It first considers the rationale for the revision of the KJV and the proposals for revision, along with the rules that were devised to govern the process of revision. It then assesses the reception of the Revised Version of the New Testament before turning to a discussion of the revision of the Old Testament and of the Revised Version of the KJV. Finally, it examines whether the Revised Version of the KJV can be viewed as a modernisation of the KJV or as a new version of the Bible.
Cognitive Fusion and Pain Experience in Young People
Authors: Solé Ester , Tomé-Pires Catarina , de la Vega Rocío , Racine Mélanie , Castarlenas Elena , Jensen Mark P. , Miró Jordi
Published: March 2015

Objectives:

Acceptance and Commitment Therapy (ACT) has been shown to be an effective treatment for chronic pain in young people. Cognitive fusion is a key concept of ACT that is hypothesized to contribute to distress and suffering. In this study, we sought to: (1) test hypothesized associations between cognitive fusion and pain intensity, disability, and catastrophizing; and (2) examine the function of cognitive fusion as a possible mediator between catastrophizing and disability.

Methods:

A community sample of 281 young people (11 to 20 y) completed measures assessing cognitive fusion, pain intensity, disability, and pain catastrophizing.

Results:

Cognitive fusion was positively related to pain intensity (r=0.24, P<0.01), disability (r=0.32, P<0.001), and pain catastrophizing (r=0.47, P<0.001). Moreover, cognitive fusion was found to mediate the association between pain catastrophizing and disability (β=0.01, 95% confidence interval=0.002-0.024, 5000 bootstrap resamples).

Discussion:

The findings indicate that cognitive fusion is moderately to strongly associated with pain-related outcomes, which support the need for further research to (1) better understand the relationship between cognitive fusion and adjustment to chronic pain, and (2) determine whether the benefits of treatments such as ACT are mediated, at least in part, by reductions in cognitive fusion.
Celiac Disease Alone and Associated With Type 1 Diabetes Mellitus
Authors: Tsouka Alexandra , Mahmud Farid H. , Marcon Margaret A.
Published: March 2015

Objectives:

The aim of the study was to evaluate complication screening and follow‐up patterns in a population with type 1 diabetes mellitus and celiac disease (T1D/CD) in relation to a matched cohort with celiac disease (CD) alone at our center.

Methods:

We retrospectively reviewed the health charts of 41 children with T1D and biopsy‐proven CD and compared anthropometrics and complication of screening within 2 years from CD diagnosis. Follow‐up patterns were determined 3 years postdiagnosis. This population was then compared with a population with both symptomatic and asymptomatic CD matched for age and sex.

Results:

In comparison with T1D/CD, patients with CD alone had a significantly lower height, weight and body mass index (BMI z score 0.01 vs 0.81, P = 0.001) and higher rates of screening for anemia (95% vs 71%, P = 0.003) and bone health (49% vs 29%, P = 0.05). Minimal rates of laboratory abnormalities were observed in either group, irrespective of symptoms at presentation, but CD alone more often presented with anemia than T1D/CD. Repeat serology testing was significantly more frequently performed in the T1D/CD group. Follow‐up was equally variable with a median of 3 (range 0–4) visits with a gastroenterologist during the first 3 years postdiagnosis.

Conclusions:

These results suggest that patients with T1D/CD represent a distinct and possibly milder phenotype from CD alone. Complication screening was variable and negative for the majority of the patients. Guidelines for follow‐up may need to be tailored to specific groups to standardize evaluation and complication screening, especially with regard to bone health.
A Measure of Barriers Toward Medical Disclosure Among Health Professionals in the United Arab Emirates
Authors: Zaghloul Ashraf Ahmad , Elsergany Moetaz , Mosallam Rasha
Published: March 2015

Background

There has been a growing awareness that patients are subject to injuries that can be prevented as a direct consequence of health care. Error disclosure is an effective technique to restore the lost trust with the health care system.

Objective

The current study aimed to develop a valid and reliable scale to determine the factors facilitating the disclosure of health professionals in health organizations.

Methods

This study had a cross-sectional design that consisted of 722 responses (response rate of 68.3%) from 1 private and 1 public hospital in Sharjah, United Arab Emirates. The data collection tool included 23 items rated on a Likert scale ranging from 5, strongly agree, to 1, strongly disagree.

The internal consistency was established through calculating the split-half reliability for part 1 (12 items), which had a Cronbach coefficient of 0.65, and part 2 (11 items), which had a Cronbach coefficient of 0.62. Scale validity was assessed with the Kaiser-Meyer-Olkin measure of sampling adequacy, which had a value of 0.62, and the Bartlett test of sphericity (approximated χ2 = 13012.2, P = 0.0001) supported the factorability of the correlation matrix. The varimax rotation revealed 5 components that explained 77.8% of the total variance.

Results

The varimax rotation revealed 21 items loaded on the following 5 factors: fear of disclosure and provider image consequences (factor 1), apology (factor 2), organizational culture toward patient safety (factor 3), professional ethics and transparency (factor 4), as well as patient and provider education (factor 5).

Conclusions

The disclosure of medical mistakes requires preliminary considerations to effectively and compassionately disclose these events to patients. The validity and reliability of the results support the use of this scale at hospitals as part of the health care providers' disclosure processes.
Impact of Inpatient Harms on Hospital Finances and Patient Clinical Outcomes
Authors: Adler Lee , Yi David , Li Michael , McBroom Barry , Hauck Loran , Sammer Christine , Jones Cason , Shaw Terry , Classen David
Published: March 2015

Objective

The aim of this study was to determine the impact of all-cause inpatient harms on hospital finances and patient clinical outcomes.

Research Design

A retrospective analysis of inpatient harm from 24 hospitals in a large multistate health system was conducted during 2009 to 2012 using the Institute of Healthcare Improvement Global Trigger Tool for Measuring Adverse Events. Inpatient harms were detected and categorized into harm (F–I), temporary harm (E), and no harm.

Results

Of the 21,007 inpatients in this study, 15,610 (74.3%) experienced no harm, 2818 (13.4%) experienced temporary harm, and 2579 (12.3%) experienced harm. A patient with harm was estimated to have higher total cost ($4617 [95% confidence interval (CI), $4364 to 4871]), higher variable cost ($1774 [95% CI, $1648 to $1900]), lower contribution margin (−$1112 [95% CI, −$1378 to −$847]), longer length of stay (2.6 d [95% CI, 2.5 to 2.8]), higher mortality probability (59%; odds ratio, 1.4 [95% CI, 1.0 to 2.0]), and higher 30-day readmission probability (74.4%; odds ratio, 2.9 [95% CI, 2.6 to 3.2]). A patient with temporary harm was estimated to have higher total cost ($2187 [95% CI, $2008 to $2366]), higher variable cost ($800 [95% CI, $709 to $892]), lower contribution margin (−$669 [95% CI, −$891 to −$446]), longer length of stay (1.3 d [95% CI, 1.2 to 1.4]), mortality probability not statistically different, and higher 30-day readmission probability (54.6%; odds ratio, 1.2 [95% CI, 1.1 to 1.4]). Total health system reduction of harm was associated with a decrease of $108 million in total cost, $48 million in variable cost, an increase of contribution margin by $18 million, and savings of 60,000 inpatient care days.

Conclusions

This all-cause harm safety study indicates that inpatient harm has negative financial outcomes for hospitals and negative clinical outcomes for patients.
A study in sums of products
Authors: Fouvry Étienne , Kowalski Emmanuel , Michel Philippe
Published: March 2015

We give a general version of cancellation in exponential sums that arise as sums of products of trace functions satisfying a suitable independence condition related to the Goursat–Kolchin–Ribet criterion, in a form that is easily applicable in analytic number theory.
On a question of Rudnick: do we have square root cancellation for error terms in moment calculations?
Authors: Katz Nicholas M.
Published: March 2015

We answer a question of Rudnick, largely in the negative, as to whether we have square root cancellation for error terms in moment calculations.
Selective strolls: fixation and extinction in diploids are slower for weakly selected mutations than for neutral ones
Authors: mafessoni fabrizio , Lachmann Michael
Published: March 2015

In finite populations, an allele disappears or reaches fixation due to two main forces, selection and drift. Selection is generally thought to accelerate the process: a selected mutation will reach fixation faster than a neutral one, and a disadvantageous one will quickly disappear from the population. We show that even in simple diploid populations, this is often not true. Dominance and recessivity unexpectedly slow down the evolutionary process for weakly selected alleles. In particular, slightly advantageous dominant and mildly deleterious recessive mu- tations reach fixation more slowly than neutral ones. This phenomenon determines genetic signatures opposite to those expected under strong selection, such as increased instead of decreased genetic diversity around the selected site. Furthermore, we characterize a new phenomenon: mildly deleterious recessive alleles, thought to represent the vast majority of newly arising mutations, survive in a population longer than neutral ones, before getting lost. Hence, natural selection is less effective than previously thought in getting rid rapidly of slightly negative mutations, contributing their observed persistence in present populations. Consequently, low frequency slightly deleterious mutations are on average older than neutral ones.
Dynamic signal processing by ribozyme-mediated RNA circuits to control gene expression
Authors: Shen Shensi , Rodrigo Guillermo , Prakash Satya , Majer Eszter , Landrain Thomas E. , Kirov Boris , Daròs José-Antonio , Jaramillo Alfonso
Published: March 2015

Organisms have different circuitries that allow converting signal molecule levels to changes in gene expression. An important challenge in synthetic biology involves thede novodesign of RNA modules enabling dynamic signal processing in live cells. This requires a scalable methodology for sensing, transmission, and actuation, which could be assembled into larger signaling networks. Here, we present a biochemical strategy to design RNA-mediated signal transduction cascades able to sense small molecules and small RNAs. We design switchable functional RNA domains by using strand-displacement techniques. We experimentally characterize the molecular mechanism underlying our synthetic RNA signaling cascades, show the ability to regulate gene expression with transduced RNA signals, and describe the signal processing response of our systems to periodic forcing in single live cells. The engineered systems integrate RNA-RNA interaction with available ribozyme and aptamer elements, providing new ways to engineer arbitrary complex gene circuits.
Global variability in gene expression and alternative splicing is modulated by mitochondrial content
Authors: Guantes Raul , Rastrojo Alberto , Neves Ricardo , Lima Ana , Aguado Begoña , Iborra Francisco J.
Published: March 2015

Noise in gene expression is a main determinant of phenotypic variability. Increasing experimental evidence suggests that genome-wide cellular constraints largely contribute to the heterogeneity observed in gene products. It is still unclear, however, which global factors affect gene expression noise and to what extent. Since eukaryotic gene expression is an energy demanding process, differences in the energy budget of each cell could determine gene expression differences. Here, we quantify the contribution of mitochondrial variability (a natural source of ATP variation) to global variability in gene expression. We find that changes in mitochondrial content can account for ∼50% of the variability observed in protein levels. This is the combined result of the effect of mitochondria dosage on transcription and translation apparatus content and activities. Moreover, we find that mitochondrial levels have a large impact on alternative splicing, thus modulating both the abundance and type of mRNAs. A simple mathematical model in which mitochondrial content simultaneously affects transcription rate and splicing site choice can explain the alternative splicing data. The results of this study show that mitochondrial content (and/or probably function) influences mRNA abundance, translation, and alternative splicing, which ultimately affects cellular phenotype.
Sumoylation of Rap1 mediates the recruitment of TFIID to promote transcription of ribosomal protein genes
Authors: Chymkowitch Pierre , Nguéa P Aurélie , Aanes Håvard , Koehler Christian J. , Thiede Bernd , Lorenz Susanne , Meza-Zepeda Leonardo A. , Klungland Arne , Enserink Jorrit M.
Published: March 2015

Transcription factors are abundant Sumo targets, yet the global distribution of Sumo along the chromatin and its physiological relevance in transcription are poorly understood. Using Saccharomyces cerevisiae, we determined the genome-wide localization of Sumo along the chromatin. We discovered that Sumo-enriched genes are almost exclusively involved in translation, such as tRNA genes and ribosomal protein genes (RPGs). Genome-wide expression analysis showed that Sumo positively regulates their transcription. We also discovered that the Sumo consensus motif at RPG promoters is identical to the DNA binding motif of the transcription factor Rap1. We demonstrate that Rap1 is a molecular target of Sumo and that sumoylation of Rap1 is important for cell viability. Furthermore, Rap1 sumoylation promotes recruitment of the basal transcription machinery, and sumoylation of Rap1 cooperates with the target of rapamycin kinase complex 1 (TORC1) pathway to promote RPG transcription. Strikingly, our data reveal that sumoylation of Rap1 functions in a homeostatic feedback loop that sustains RPG transcription during translational stress. Taken together, Sumo regulates the cellular translational capacity by promoting transcription of tRNA genes and RPGs.
Crystal structure of ethyl 2-cyano-3-[(1-ethoxyethylidene)amino]-5-(3-methoxyphenyl)-7-methyl-5H-1,3-thiazolo[3,2-a]pyrimidine-6-carboxylate
Authors: Krishnamurthy M. S. , Begum Noor Shahina
Published: March 2015

In the title compound, C22H24N4O4S, the central pyrimidine ring adopts a sofa conformation with the ring-junction N atom displaced by 0.2358 (6) Å from the mean plane of the remaining ring atoms. The 3-methoxyphenyl ring, at the chiral C atom opposite the other N atom, is positioned axially and is inclined to the thiazolopyrimidine ring with a dihedral angle of 83.88 (7)°. The thiazole ring is essentially planar (r.m.s. deviation = 0.0034 Å). In the crystal, pairs of weak C—H...O hydrogen bonds link molecules related by twofold rotation axes to formR22(8) rings, which in turn are linked by weak C—H...N interactions, forming ribbons along [-110]. In addition, π–π stacking interactions [centroid—centroid distance = 3.5744 (15) Å] connect the ribbons, forming slabs lying parallel to (001).
“Safe handover saves lives”: results from clinical audit
Authors: Advani Rajeev , Stobbs Nicola Marie , Killick Neil , Kumar B Nirmal
Published: March 2015

Purpose

– The implementation of the European Working Time Directive and its subsequent impact on the hours worked by doctors in training has resulted in shift-working rotas being the norm and greater cross-cover between specialties. As such, the need for continuity of information and comprehensiveness of handover between shifts has become more important than ever. The purpose of this paper is to show how handover can be improved by the implementation of an electronic handover system and subsequent Quality Improvement Rapid Cycle Change Model of clinical audit.

Design/methodology/approach

– Initial data were collected using a standardised questionnaire collected prospectively from all junior doctors within the surgical division. Following the first audit cycle, changes were implemented in a Quality Improvement Rapid Cycle Change Model of clinical audit and a Surgical Division Electronic Handover Shared Drive was developed. Three further prospective cycles of clinical audit were carried out over a period of 12 months.

Findings

– The results show a more effective handover system to be in place. Effects of change measured as an 80 per cent standard was achieved in all categories and maintained throughout all cycles of re-audit.

Practical implications

– A surgical division shared electronic handover drive was developed and subsequent audits have shown improved handover practice in a foundation trust. This has positive benefits on patient safety and quality of care.

Originality/value

– This work is of interest to those looking to set up an electronic handover system and additionally to all those working in specialities where cross-cover is required.
Modelling banking-hall yield for property investment
Authors: Tipping Malvern , Newton Roger
Published: March 2015

Purpose

– This paper aims to build a predictive model for the investment yield of British banking-halls.

Design/methodology/approach

– Empirical data of similar lots sold at previous auctions are subjected to statistical analyses utilizing a cross-sectional research design. The independent variables analysed are taken from a previous study using the same cases. Models are built using logistic regression and ANCOVA.

Findings

– Logistic regression generally generates better models than ANCOVA. A division of Britain on a north/south divide produces the best results. Rent is as good as lot size and price in modelling, but has greater utility, because it is known prior to auctions.

Research limitations/implications

– Cases analysed were restricted to lots let entirely as banking-halls. Other lots comprising premises only partially used as banking-halls might produce different results. Freehold was the only tenure tested.

Practical implications

– The study provides a form of predictive modelling for investors and their advisors using rent which is known in advance of any sale.

Originality/value

– The study makes an original contribution to the field, because it builds a predictive model for investment yields for this class of property. Further research may indicate if similar predictive models can be built for other classes of investment property.
The effect of family ownership and control on equity-based compensation
Authors: Baek Hyungkee Young , Fazio Philip L
Published: March 2015

Purpose

– Small public family firms apply contracting differently given the peculiar motivations of founding families and the degree to which they monitor operations. The purpose of this paper is to examine the effects of family ownership, control, and CEO dividends on CEO incentive compensation.

Design/methodology/approach

– The sample consisted of 194 firms, covering about 40 percent of the relevant S&P SmallCap 600 firms. Employed were a logistic regression of the presence of incentive compensation plan and a panel regression of incentive compensation ratio against the family ownership, family CEO, CEO ownership, and dividend income variables as well as firm-specific and CEO-specific control variables.

Findings

– For 1,532 firm-year observations among S&P SmallCap600 index firms during 1999-2007, the authors found that family ownership and CEO dividend income ratio negatively related to the likelihood of an incentive compensation plan and to the ratio of equity-based compensation to total CEO pay. Additionally, the effect of CEO dividend income was limited to firms with outside CEOs.

Practical implications

– Boards of small capitalization firms should consider the incentive effects of CEO dividend income and CEO family membership when setting their compensation policies.

Originality/value

– S&P SmallCap600 index firms are unique because they are much smaller than those listed in the S&P 500 or theFortune500, and are subject to more family influence. SmallCap firms are comparable in size to the foreign firms previously researched but are still well covered by analysts, and benefit from audited financial statement variables, which include dividends and stock market returns.
Father-daughter succession in China: facilitators and challenges
Authors: Deng Xin
Published: March 2015

Purpose

– The purpose of this paper is to explore factors facilitating and impeding succession from father to daughter in family businesses in China.

Design/methodology/approach

– Using explorative case study approach this study examines the experiences of four female successors at different stages of taking over family businesses.

Findings

– Contrary to previous studies on female succession, daughters in this study were groomed to run the family business, and encouraged to become involved in it at an early stage. Confucian values on parent-child relationships and family also encouraged daughters’ participation in the family business and in maintaining productive working relationships with their fathers. However, inheriting and maintaining a father’s Guanxi networks pose a daunting challenge for daughters, and daughters may need more time to establish their authority.

Originality/value

– While confined by the limited number of cases, this study contributes to the under-explored research area of father-daughter succession by highlighting some unique cultural, social and historical factors influencing female successors in the Chinese context.
Family businesses: seekers of advice
Authors: Reddrop Alan , Mapunda Gido
Published: March 2015

Purpose

– The purpose of this paper is to increase understanding of the often questioned willingness of family businesses (FBs) to seek external advice on challenges they face.

Design/methodology/approach

– Mixed methods were employed gaining 140 responses to a survey of FB CEOs on their use of advice, followed by 51 semi-structured interviews of FB owners, managers and advisers. It drew upon institutional theory and those concerning both trust and organisational knowledge creation; also upon experiential knowledge gained in advising FBs.

Findings

– Cost was found to deter use of professional advice, also unawareness of where it was to be found. Dissatisfaction with many advisers’ “soft” skills was prevalent. Clients took as given advisers’ technical knowledge; empathy and listening skills being the discriminants of successful practice. Effective means of skills creation were identified but seen to be obtained fortuitously, not systematically. The professional institutions of accountants, the most frequently used professional advisers, require tertiary institutions seeking their accreditation to develop their students’ “generic skills”, including “the ability to listen effectively”: conditions not being complied with. However, advice-seeking is found to be greater than assumed because of an unexpected resort to peers, often through networking. Widespread peers’ recommendations of professional advisers impart instantaneous “vicarious” trust, found to be more common than the “slow maturing” kind posited by previous researchers.

Originality/value

– This paper offers a rarely recorded FB client perspective on their use of external advice. It extends understanding of the trust upon which they rely. It discloses how some achieve a mutual learning that expands understanding of organisational knowledge creation. It describes a route, “shadowing”, through which professional advisers have achieved outstanding performance.
How the new generation of consoles have accelerated the need to preserve digital content – part 2
Authors: McEniry Matthew , Cassidy Ryan
Published: March 2015

Purpose

– This two-part paper aims to expose the challenges and establish the necessity of preserving digital content, with a focus on console video games. Part two identifies the preservation challenges, methods of preserving digital content and the current efforts by preservation groups and organizations.

Design/methodology/approach

– Through a method of identifying a video game content which has been lost, or at risk of being lost, describing the challenges presented by the format, and addressing the current preservation efforts, this paper serves as a brief retrospective of the issues and a guide to extending the conversation.

Findings

– While preserving video game content faces many challenges due to copyright issues and risks associated with digital format, some institutions have made progress that other libraries can follow.

Originality/value

– With special attention to the non-gamer, the conversation on video game preservation continues by focusing on the challenges and current efforts.
Laying the groundwork for information literacy at a research university
Authors: Castro Gessner A. Gabriela , Eldermire Erin
Published: March 2015

Purpose

– Information literacy (IL) is increasingly becoming an explicit learning outcome for college graduates, and some libraries are playing a role in planning and teaching IL instruction to students. Amidst the overall trend of shrinking budgets that libraries are experiencing, what strategies can be employed by libraries that support large universities to plan IL instruction? The paper aims to discuss these issues.

Design/methodology/approach

– Inspired by curriculum mapping, staff in the library assessment department created teaching maps which match the curriculum from seven colleges with the library’s teaching efforts. To create them, they combined information about: first, courses that librarians have instructed over the last three years with; second, required courses for majors within the colleges; and third, typical enrollment for each course.

Findings

– Easily accessible information was combined to create the teaching maps, which enable the library to realign efforts to maximize IL instruction and best utilize library staff resources.

Practical implications

– Teaching maps serve as a portal to quickly understand majors, courses and course enrollment, and provide baseline information on past library instruction activity to inform future IL instruction strategy. Library directors and teaching staff are utilizing them to realign instruction efforts.

Originality/value

– Assessment strategies, such as curriculum mapping, serve not only the institution’s teaching mission, but also help strategize for effective and efficient stewardship of staff resources. These methods will be useful for library directors, assessment and instruction librarians at large research universities.
Serum heparanase levels: A protective marker against digital ulcers in patients with systemic sclerosis
Authors: Wu Ching‐Ying , Asano Yoshihide , Taniguchi Takashi , Sato Shinichi , Yu Hsin‐Su
Published: March 2015

Heparanase is an endo‐β‐D‐glucuronidase cleaving heparan sulfate side‐chains of heparin sulfate proteoglycans, which is involved in wound healing, inflammation, neovascularization and tumor progression through the degradation and remodeling of the extracellular matrix and the release of sequestered pro‐angiogenic factors. Because heparanase‐mediated biological processes seem to be involved in the development of systemic sclerosis (SSc), we investigated the clinical correlation of serum heparanase levels in patients with this disease. Serum heparanase levels were significantly higher in SSc patients than in healthy individuals, while comparable between diffuse cutaneous SSc and limited cutaneous SSc subgroups. On the other hand, SSc patients with digital ulcers had serum heparanase levels significantly lower than those without. These results suggest that serum heparanase levels may be elevated in SSc patients reflecting the contribution of heparanase‐dependent biological processes to the development of SSc. SSc patients with high serum heparanase levels may be protected from the development of digital ulcers due to the increased release of sequestered pro‐angiogenic factors such as vascular endothelial growth factor. Therefore, serum heparanase levels may serve as a protective marker against digital ulcers in SSc patients.
Pigmented purpuric dermatosis‐like sarcoidosis
Authors: Sezer Engin , Yalçın Özben , Erkek Emel , Şahin Sedef
Published: March 2015

Sarcoidosis is a chronic multisystem granulomatous disease of unknown origin. Recently, a purpuric variant of cutaneous sarcoidosis resembling pigmented purpuric dermatosis (PPD) has been documented. Herein, we describe another unusual case with clinical features mimicking PPD, characterized by brownish macules and flat‐topped papules with a slightly purpuric component on the legs and dorsum of the feet and histopathological features consistent with sarcoidosis. We designated this unusual clinical presentation as “PPD‐like sarcoidosis”.
Dermoscopy of prurigo nodularis
Authors: Errichetti Enzo , Piccirillo Angelo , Stinco Giuseppe
Published: March 2015

The diagnosis of prurigo nodularis is mainly clinical, based on its distinctive features. However, in some cases it may be difficult to differentiate it from other nodular dermatoses only on the clinical basis, thus requiring histopathological examination to reach a definitive diagnosis. The aim of this study was to describe for the first time the dermoscopic features of prurigo nodularis and the useful contribution of dermoscopy in the differential diagnosis of such dermatoses. Fourteen patients with histopathologically proven prurigo nodularis were included in the study. The results of our study suggest that the detection of a “white starburst pattern” surrounding brown‐reddish/brown‐yellowish crust(s), erosion(s) and/or hyperkeratosis/scales is a useful clue to support the clinical diagnosis of prurigo nodularis, distinguishing it from the other main differential diagnoses.