bluuebunny/crossref_metadata_2025 huggingface dataset:
Audiological Outcomes in Growing Vestibular Schwannomas Managed Either Conservatively, or With Stereotactic Radiosurgery
Authors: Milner Thomas Daniel , Locke Richard R. , Kontorinis Georgios , Crowther John A.
Published: January 2018

Objective:

Recent studies have suggested good hearing preservation following stereotactic radiosurgery (STRS) in patients with vestibular schwannomas (VS). This study aims to assess audiological outcomes in patients with growing VS treated either with STRS, or managed conservatively.

Study Design:

Retrospective cohort study.

Setting:

Tertiary referral center.

Patients:

Out of 540 patients with VS, 69 patients with growing VS fulfilled the inclusion criteria; 24 treated conservatively and 45 with STRS. VS were considered growing if demonstrating more than 15% tumor volume increase during 1 year of watchful waiting.

Intervention:

American Association of Otolaryngology–Head and Neck Surgery (AAOHNS) hearing threshold (dB averaged over 500–3000 Hz) deterioration and Gardner–Robertson class deterioration over time were used as the primary outcome measures. Rate of progression to loss of functional hearing (Gardner–Robertson class I–II) was also determined between cohorts.

Results:

Mean follow-up was similar between treatment cohorts (STRS = 69.6 mo, conservative management = 71.7 mo). There was no significant difference in AAOHNS deterioration (t = 1.05, df = 53, p = 0.301) or Gardner–Robertson deterioration (χ
2 = 0.47, df = 1, p = 0.492) between cohorts. Furthermore, rate of progression to loss of functional hearing was similar between cohorts (Hazard ratio = 0.704, 95% CI 0.287–1.728, p = 0.44). In STRS patients, AAOHNS deterioration was greater in those with lower AAOHNS thresholds at diagnosis (t = –2.683, df = 28, p = 0.0121). Similarly, Gardner–Robertson deterioration was significantly more likely in STRS patients with functional hearing (Gardner–Robertson class I–II) (Adjusted odds ratio = 32.14, 95% CI 3.15–328, p = 0.0034).

Conclusions:

STRS results in similar audiological outcomes compared with patients managed conservatively; Consequently, STRS given to patients with VS to preserve hearing is not justified. In contrast to recent studies, patients with preserved hearing at diagnosis have significantly greater audiological deterioration when undergoing STRS.
Long-Term Hearing Preservation Outcomes for Small Vestibular Schwannomas: Retrosigmoid Removal Versus Observation
Authors: Zhu Weidong , Chen Hongsai , Jia Huan , Chai Yongchuan , Yang Jie , Wang Zhaoyan , Wu Hao
Published: January 2018

Objective:

Management of small vestibular schwannomas (VSs) consists of three options: serial observation, radiosurgery, and microsurgery. The authors reported the long-term hearing outcomes after retrosigmoid tumor removal in 110 patients and hearing follow-up outcomes in 160 serial observation patients with small VSs to explore the appropriate management strategy and predictive factors of hearing preservation for small VSs.

Study Design:

Retrospective study.

Setting:

Tertiary referral center.

Patients:

In this study, 110 patients with small VS (purely intracanalicular/cerebellopontine angle tumor ≤15 mm) during a 15-year period, from January 2001 to December 2015, were candidates for hearing preservation surgery through retrosigmoid approach, while 160 patients were candidates for serial observation. The main outcome measure was preservation of hearing under different hearing levels, assessed with the classification of American Academy of Otolaryngology–Head and Neck Surgery.

Results:

Preoperative hearing levels of the 110 study patients were Class A in 49 patients, Class B in 43 patients, and Class C in 18 patients. In all surgery patients (n = 110), 97.3% (107/110) patients maintained the same level during postoperative follow-up (mean follow-up time was 49.1 ± 28.2 mo) and 86 (78.2%) had complete radiologic and audiometric data at least 4 years follow-up for review. In the 4 years follow-up surgery group (n = 86), postoperative hearing levels were Class A, B, C, and D for 22, 11, 18, and 35 patients, and postoperative rates of preservation of serviceable and useful hearing were 59.3% (51/86) and 47.1% (33/70), respectively. In serial observation group, mean follow-up time was 35.2 ± 33.1 months; mean tumor size at presentation was 8.6 ± 4.3 mm; overall mean tumor growth rate was 1.08 ± 2.3 mm/yr; serviceable hearing preservation rate of 98 patients was 54.1% (53/98) at the 5-year end point and 48.7% (37/76) at the 7-year end point.

Conclusion:

Tumor removal should be the first treatment option for patients with small VSs and preserved hearing, especially for young patients with good hearing; retrosigmoid approach is an effective and safe approach for small VSs removal with excellent functional outcomes; better preoperative hearing predicted a higher rate of postoperative hearing preservation; patients without fundal extension were more likely to achieve hearing preservation than those with fundal extension, but no difference had been detected when retrosigmoid removal assisted with endoscope was performed; patients with small tumors originating from SVN were more likely to achieve hearing preservation compared with those with IVN-originating tumors.
Vestibular Function and Gross Motor Development in 195 Children With Congenital Hearing Loss—Assessment of Inner Ear Malformations
Authors: Kimura Yusuke , Masuda Takeshi , Kaga Kimitaka
Published: January 2018

Objectives:

To evaluate the relationship between vestibular function and gross motor development in children with inner ear malformations.

Methods:

A total of 195 children (average age: 2.4 ± 1.6 yr) with profound hearing loss, defined as a hearing threshold greater than 80 dB, participated in this study. Evaluation of vestibular function was assessed in all children using a damped rotational chair test. Gross motor development was assessed by examining the age of acquisition of head control and independent walking. Temporal bone computed tomography scans were conducted in 190 of the 195 children.

Results:

Among the 195 children, 31 children (15.9%) showed a reduced response in the rotational chair test. Of the 17 children who were followed up with repeat rotational chair tests, 16 showed more obvious nystagmus during follow-up compared with the initial examination. The reduced response group showed significant delays in head control and independent walking compared with the normal response group (p < 0.01). Forty-one children (21.6%) demonstrated inner ear malformations and showed significantly delayed acquisition of head control and independent walking (p < 0.01) compared with children with normal vestibular function. Children with inner ear malformations with a reduced response in the rotational chair test had severe vestibular (p < 0.05) and lateral semicircular canal (p < 0.01) malformations as the most common findings.

Conclusions:

Structural inner ear malformations are associated with vestibular dysfunction and delayed gross motor development. Our findings confirm that there is a higher incidence of reduced vestibulo-ocular reflex in children with vestibular and semicircular canal malformations.
Characteristics and comorbidities of inpatients without celiac disease on a gluten-free diet
Authors: Blackett John W. , Shamsunder Meghana , Reilly Norelle R. , Green Peter H.R. , Lebwohl Benjamin
Published: January 2018

Objectives

Despite the increasing popularity of gluten-free diet (GFD), the demographic characteristics and medical features of patients without celiac disease on this diet have not been extensively investigated.

We aimed to characterize the medical conditions and demographic backgrounds of hospitalized patients without celiac disease who adhere to a GFD, to further understand their reasons for gluten avoidance.

Materials and methods

We performed an observational cohort study on all inpatients at Columbia University Medical Center on a GFD in 2011–2016, excluding those with celiac disease, compared with age-matched and sex-matched inpatients on a regular diet. We determined the odds ratio (OR) of being on a GFD for various comorbidities using conditional logistic regression.

Results

Of 769 inpatients on a GFD, most (63.6%) did not have celiac disease. Gluten-avoiding patients were more likely to be non-Hispanic Whites [OR: 2.92; 95% confidence interval (CI): 2.31–3.70]. They had a lower prevalence of hypertension (OR: 0.38; 95% CI: 0.27–0.52) and diabetes (OR: 0.58; 95% CI: 0.32–0.75) and higher prevalence of inflammatory bowel disease (OR: 1.56; 95% CI: 1.02–2.41), irritable bowel syndrome (OR: 6.16; 95% CI: 2.11–10.23), hyperthyroidism (OR: 2.73; 95% CI: 1.22–6.10), hypothyroidism (OR: 2.06; 95% CI: 1.39–3.06), lupus (OR: 2.87; 95% CI: 1.13–7.29), and autism spectrum disorder (OR: 23.42; 95% CI: 5.29–103.73).

Conclusion

Nonceliac gluten-avoiding patients have higher prevalences of inflammatory bowel disease, irritable bowel syndrome, thyroid disease, lupus, and autism spectrum disorder, suggesting patients with these disorders have turned to a GFD for perceived benefit, despite a scant evidence basis.
Thermoelectric magnetohydrodynamic effects on the crystal growth rate of undercooled Ni dendrites
Authors: Kao A. , Gao J. , Pericleous K.
Published: January 2018

In the undercooled solidification of pure metals, the dendrite tip velocity has been shown experimentally to have a strong dependence on the intensity of an external magnetic field, exhibiting several maxima and minima. In the experiments conducted in China, the undercooled solidification dynamics of pure Ni was studied using the glass fluxing method. Visual recordings of the progress of solidification are compared at different static fields up to 6 T. The introduction of microscopic convective transport through thermoelectric magnetohydrodynamics is a promising explanation for the observed changes of tip velocities. To address this problem, a purpose-built numerical code was used to solve the coupled equations representing the magnetohydrodynamic, thermal and solidification mechanisms. The underlying phenomena can be attributed to two competing flow fields, which were generated by orthogonal components of the magnetic field, parallel and transverse to the direction of growth. Their effects are either intensified or damped out with increasing magnetic field intensity, leading to the observed behaviour of the tip velocity. The results obtained reflect well the experimental findings.

This article is part of the theme issue ‘From atomistic interfaces to dendritic patterns’.
Thermo-solutal and kinetic modes of stable dendritic growth with different symmetries of crystalline anisotropy in the presence of convection
Authors: Alexandrov Dmitri V. , Galenko Peter K. , Toropova Lyubov V.
Published: January 2018

Motivated by important applications in materials science and geophysics, we consider the steady-state growth of anisotropic needle-like dendrites in undercooled binary mixtures with a forced convective flow. We analyse the stable mode of dendritic evolution in the case of small anisotropies of growth kinetics and surface energy for arbitrary Péclet numbers and
n
-fold symmetry of dendritic crystals. On the basis of solvability and stability theories, we formulate a selection criterion giving a stable combination between dendrite tip diameter and tip velocity. A set of nonlinear equations consisting of the solvability criterion and undercooling balance is solved analytically for the tip velocity
V
and tip diameter
ρ
of dendrites with
n
-fold symmetry in the absence of convective flow. The case of convective heat and mass transfer mechanisms in a binary mixture occurring as a result of intensive flows in the liquid phase is detailed. A selection criterion that describes such solidification conditions is derived. The theory under consideration comprises previously considered theoretical approaches and results as limiting cases. This article is part of the theme issue ‘From atomistic interfaces to dendritic patterns’.

This article is part of the theme issue ‘From atomistic interfaces to dendritic patterns’.
Nonlinear dynamics of mushy layers induced by external stochastic fluctuations
Authors: Alexandrov Dmitri V. , Bashkirtseva Irina A. , Ryashko Lev B.
Published: January 2018

The time-dependent process of directional crystallization in the presence of a mushy layer is considered with allowance for arbitrary fluctuations in the atmospheric temperature and friction velocity. A nonlinear set of mushy layer equations and boundary conditions is solved analytically when the heat and mass fluxes at the boundary between the mushy layer and liquid phase are induced by turbulent motion in the liquid and, as a result, have the corresponding convective form. Namely, the ‘solid phase–mushy layer’ and ‘mushy layer–liquid phase’ phase transition boundaries as well as the solid fraction, temperature and concentration (salinity) distributions are found. If the atmospheric temperature and friction velocity are constant, the analytical solution takes a parametric form. In the more common case when they represent arbitrary functions of time, the analytical solution is given by means of the standard Cauchy problem. The deterministic and stochastic behaviour of the phase transition process is analysed on the basis of the obtained analytical solutions. In the case of stochastic fluctuations in the atmospheric temperature and friction velocity, the phase transition interfaces (mushy layer boundaries) move faster than in the deterministic case. A cumulative effect of these noise contributions is revealed as well. In other words, when the atmospheric temperature and friction velocity fluctuate simultaneously due to the influence of different external processes and phenomena, the phase transition boundaries move even faster. This article is part of the theme issue ‘From atomistic interfaces to dendritic patterns’.

This article is part of the theme issue ‘From atomistic interfaces to dendritic patterns’.
Expression variation and covariation impair analog and enable binary signaling control
Authors: Kovary Kyle M. , Taylor Brooks , Zhao Michael L. , Teruel Mary N.
Published: January 2018

Due to noise in the synthesis and degradation of proteins, the concentrations of individual vertebrate signaling proteins were estimated to vary with a coefficient of variation (CV) of approximately 25% between cells. This high variation enables population-level regulation of cell functions but abolishes accurate single-cell signal transmission. Here we measure cell-to-cell variability of relative protein abundance using quantitative proteomics of individual Xenopus laevis eggs and cultured human cells and show that variation is typically much lower, in the range of 5–15%, compatible with accurate single-cell transmission. Furthermore, we show that MEK and ERK expression covary which improves controllability of the fraction of cells that activate bimodal ERK signaling, arguing that covariation has a role in facilitating population-level control of binary cell-fate decisions. Together, our experimental and model data argues for a control principle whereby low covariation limits signaling noise for accurate control analog single-cell signaling. In contrast, increased covariation widens the stimulus-range over which external inputs can regulate binary cell activation, thereby enabling accurate control of the fraction of activated cells at the population level.
Functional mapping of the mousehairlessgene promoter region
Authors: Folco Eric G. , Nonchev Stefan
Published: January 2018

The mousehairlessgene (Hr) encodes a protein of 127 kDa, acting as corepressor of nuclear hormone receptors. The Hairless protein (HR) is involved in the control of the cellular transition to the first hair cycle in adult Mammals. In its absence hair follicles disintegrate leading to a complete and irreversible hair loss with formation of cutaneous cysts. The hairless phenotype is therefore linked to defective proliferation and migration of the hair follicle stem cells apparently unable to respond to various signalling molecules. TheHrgene is expressed at high levels in skin and brain, andhairlesstranscripts were detected in gonads, thymus and colon. Although the patterns ofHrexpression appear to be spatially and temporally regulated, very little is known about the molecular basis of the transcriptional control underlyingHrgene function. In this work we determine the precise transcriptional initiation start site of the mouseHrgene and identify a new 1,1 kb cis-control element (RE1) that encompasses the promoter region and is able to drive luciferase reporter expression in skin and brain derived cell lines. We performed a deletion analysis and explored functionally regulatory motifs within this fragment to show that the role of this upstream regulatory region is linked to the presence of TRE and VDRE binding sites. We find that a TRE situated at –300 bp from the cap site is essential for gene expression in both skin NIH 3T3 and GHFT1 cells, while a VDRE positioned 94 bp upstream of the TRE modulates reporter expression specifically in skin derived cell lines. In addition, we define a novel cis-regulatory motif UE60, situated at the 5’-end of RE1 and likely to interact with both TRE and VDRE. Our data complete previous results on the possible existence of an autoregulatory pathway, implicated inHrgene regulation. Taken together these findings reveal a complex molecular network that potentially links several signalling pathways in hair follicle formation. We discuss the organisation of the regulatory modules in the mouseHrgene upstream DNA sequences in the light of the high homology of this region in mouse, rat and human.
HOTAIRprimes the Ewing sarcoma family of tumors for tumorigenesis via epigenetic dysregulation involving LSD1
Authors: Siddiqui Hasan , Selich-Anderson Julia , Felgenhauer Joshua , Fitch James , Nadella Vijay , Taslim Cenny , Tomino Laura , Theisen Emily , Otsuru Satoru , Horwitz Edwin , Lessnick Stephen , White Peter , Shah Nilay
Published: January 2018

The EWS-FLI1 fusion protein drives oncogenesis in the Ewing sarcoma family of tumors (ESFT) in humans, but its toxicity in normal cells requires additional cellular events for oncogenesis. We show that the lncRNAHOTAIRmaintains cell viability in the presence of EWS-FLI1 and redirects epigenetic regulation in ESFT.HOTAIRis consistently overexpressed in ESFTs and is not driven by EWS-FLI1. Repression ofHOTAIRin ESFT cell lines significantly reduces anchorage-independent colony formation in vitro and impairs tumor xenograft growth in vivo. Overexpression ofHOTAIRin human mesenchymal stem cells (hMSCs), a putative cell of origin of ESFT, and IMR90 cells induces colony formation. Critically, HOTAIR-expressing hMSCs and IMR90 cells remain viable with subsequentEWS-FLI1expression.HOTAIRinduces histone modifications and gene repression through interaction with the epigenetic modifier LSD1 in ESFT cell lines and hTERT-hMSCs. Our findings suggest thatHOTAIRmaintains ESFT viability through epigenetic dysregulation.

Significance

While theEWS-FLI1fusion gene was determined to be the oncogenic driver in the overwhelming majority of ESFT, it is toxic to cell physiology and requires one or more additional molecular events to maintain cell viability. As these tumors have surprisingly few genetic mutations at diagnosis, epigenetic changes have been considered to be such an event, but the mechanism by which these changes are driven remains unclear. Our work shows thatHOTAIRis consistently expressed among ESFT and induces epigenetic and gene expression changes that cooperate in tumorigenesis. Furthermore, expression ofHOTAIRallows for cell viability in the setting of subsequentEWS-FLI1expression. Our findings elucidate new steps of malignant transformation in this cancer and identify novel therapeutic targets.
A metal-dependent switch moderates activity of the hexameric M17 aminopeptidases
Authors: Drinkwater Nyssa , Yang Wei , Riley Blake T. , Hayes Brooke K. , Sivaraman Komagal Kannan , Malcolm Tess R. , Atkinson Sarah C. , Borg Natalie A. , Kass Itamar , Buckle Ashley M. , McGowan Sheena
Published: January 2018

The metal-dependent M17 aminopeptidases are conserved throughout all kingdoms of life. The large enzyme family is characterised by a conserved binuclear metal center and a distinctive homohexameric arrangement. To understand the mechanistic role of the hexameric assembly, we undertook an investigation of the structure and dynamics of the M17 aminopeptidase fromP. falciparum,PfA-M17. We describe a novel structure ofPfA-M17, which shows that the active sites of each trimer are linked by a dynamic loop, and that the loop movement is coupled with a drastic rearrangement of the binuclear metal center and substrate-binding pocket. Molecular dynamics simulations, supported by biochemical analyses ofPfA-M17 variants, demonstrate that this rearrangement is inherent toPfA-M17, and that the transition between the active and inactive states is part of a dynamic regulatory mechanism. Key to the mechanism is a re-modelling of the binuclear metal center, which occurs in response to a signal from the neighbouring active site, and serves to moderate the rate of proteolysis under different environmental conditions. Therefore, this work has identified the precise mechanism by which oligomerization contributes toPfA-M17 function. Further, it has described a novel role for metal cofactors in the regulation of enzymes with implications for the wide range of metalloenzymes that operate via a two-metal ion catalytic center including DNA processing enzymes and metalloproteases.
Comparative genomics ofPseudomonas syringaereveals convergent gene gain and loss associated with specialisation onto cherry (Prunus avium)
Authors: Hulin Michelle T. , Armitage Andrew D. , Vicente Joana G. , Holub Eric B. , Baxter Laura , Bates Helen J. , Mansfield John W. , Jackson Robert W. , Harrison Richard J.
Published: January 2018

Genome-wide analyses of the effector- and toxin-encoding genes were used to examine the phylogenetics and evolution of pathogenicity amongst diverse strains ofPseudomonas syringaecausing bacterial canker of cherry (Prunus avium) including pathovarsP.spv.morsprunorum(Psm) races 1 and 2,P.spv.syringae(Pss) andP.spv.avii.

Genome-based phylogenetic analyses revealedPsmraces andP.spv.aviiclades were distinct and were each monophyletic, whereas cherry-pathogenic strains ofPsswere interspersed amongst strains from other host species.

A maximum likelihood approach was used to predict effectors associated with host specialisation on cherry.Psspossesses a smaller repertoire of type III effectors but has more toxin biosynthesis clusters compared withPsmandP.spv.avii. Evolution of cherry pathogenicity was correlated with gain of genes such ashopAR1andhopBB1through putative phage transfer and horizontal transfer, respectively. By contrast, loss of theavrPto/hopABredundant effector group was observed in cherry-pathogenic clades. Ectopic expression ofhopABandhopC1triggered the hypersensitive reaction in cherry leaves, confirming computational predictions.

Cherry canker provides a fascinating example of convergent evolution of pathogenicity that is explained by the mix of effector and toxin repertoires acting on a common host.
Transcriptomic response to host and non-host plants during oviposition in two closely related moth species
Authors: Orsucci M. , Audiot P. , Nidelet S. , Dorkeld F. , Pommier A. , Vabre M. , Severac D. , Rohmer M. , Gschloessl B. , Streiff R
Published: January 2018

We present here a comprehensive analysis of the transcriptomic response to plant environments in ovipositing females of two sibling species of phytophagous moths affiliated to different host ranges: the European corn borer (ECB) and the adzuki bean borer (ABB). We first assembled and annotated a de novo reference transcriptome based on a high throughput RNA sequencing of females placed in different plant environments, then we measured differences in gene expression between ECB and ABB, and also within each moth species between environments. We further related the differentially expressed (DE) genes to the host preference in ECB and ABB and highlighted the functional categories involved. More specifically, we conducted an analysis on chemosensory genes previously characterized in ECB, ABB and other related Ostrinia species, as these genes are considered as good candidates for the host recognition before oviposition.

Overall, we recorded more DE genes in ECB than in ABB samples, what could highlight the higher strength of the host specialization in ECB compared to ABB as observed at the behavioral level. We also noticed that the genes involved in the preference for their respective host were different between ECB and ABB. At the functional level, the response to plant environment in ECB and ABB during oviposition involved many processes, including the chemosensory repertoire as expected, but also metabolism of carbohydrates, lipids, proteins, and amino acids, detoxification mechanisms and immunity.

All together, our results allowed identifying genes and functions candidates for specialization and also for the species divergence between ECB and ABB. By ad-hoc categorization, we discriminated some genes responding to the environment with similar or divergent pattern in ECB and ABB. Among them, we highlighted new lines of research like carbohydrates metabolism or virus and retrovirus dynamics.
Varicella-zoster virus CNS vasculitis and RNA polymerase III gene mutation in identical twins
Authors: Carter-Timofte Madalina E , Hansen Anders F , Mardahl Maibritt , Fribourg Sébastien , Rapaport Franck , Zhang Shen-Ying , Casanova Jean-Laurent , Paludan Søren R , Christiansen Mette , Larsen Carsten S , Mogensen Trine H
Published: January 2018

Deficiency in the cytosolic DNA sensor RNA Polymerase III was recently described in children with severe varicella zoster infection in the CNS or lungs. Here we describe a pair of monozygotic female twins, who both experienced severe recurrent CNS vasculitis caused by VZV reactivation. The clinical presentation and findings included recurrent episodes of headache, dizziness, and neurological deficits, cerebrospinal fluid with pleocytosis and intrathecal VZV antibody production, and magnetic resonance scan of the brain showing ischaemic lesions. We performed whole exome sequencing and identified a rare mutation in the Pol III subunit POLR3F. The identified R50W POLR3F mutation is predicted to be damaging by bioinformatics and when tested in functional assays, patient PBMCs exhibited impaired antiviral and inflammatory responses to the PoL III agonist Poly(dA:dT) as well as increased viral replication in patient cells compared to controls. Altogether, these cases add genetic and immunological evidence to the novel association between defects in sensing of AT-rich DNA present in the VZV genome and increased susceptibility to severe manifestations of VZV infection in the CNS in humans.

Abbreviations

CADD

combined annotation dependent depletion

CSF

cerebrospinal fluid

DOCK

dedicator of cytokinesis

IFNGR

interferon gamma receptor

MSC

mutation significance cut-off

NK

natural killer

POLIII

RNA polymerase III

SCID

severe combined immunodeficiency

TYK

tyrosine kinase

VZV

varicella zoster virus

WES

whole exome sequencing
mTOR complex 1 pathway activation in severe keratoconus; the functional implications of GWAS identified loci
Authors: Wisse Robert PL , Kuiper Jonas JW , de Veij Mestdagh Gijsbert M , Wichers Catharina GK , Hiddingh Sanne , Vazirpanah Nadia , Imhof Saskia M , Radstake Timothy RD , Broen Jasper CA
Published: January 2018

Purpose

Keratoconus (KC) is an eye condition that can lead to a severe vision loss and may warrant a corneal grafting procedure. Meta-analyses of genome wide association studies have identified several genes that confer risks for differences in corneal curvature, corneal thickness, and developing keratoconus. Currently, there is limited evidence of a functional role for the identified loci in the affected corneal tissues.

Methods

We investigated the gene expression profiles of 4 GWAS confirmed risk loci and several related pathways that function in cellular ageing and cell cycle control in corneal tissue of a discovery and replication cohort comprising in total 27 keratoconus patients, 16 healthy controls, and 21 diseased controls (failed corneal grafts).

Results

We confirmed the MTOR gene locus as differentially expressed in KC corneas in a discovery cohort Next, we replicated these results in a second cohort and found evidence of increased expression of various mTORC1 pathway signature genes, namely MTOR itself (P=0.040), AKT1 (P=0.028), IGF1R (P=0.022) and RAPTOR (P=0.007).

Conclusions

Gene expression profiling in cornea tissues revealed robust up-regulation of the mTORC1 pathway in KC and substantiates a potential role for this pathway in its pathogenesis. Functional implications should be further studied since biomarkers for disease activity are needed and selective targeting of the mTOR pathway is a promising treatment concept.
Root meristem growth factor 1 controls root meristem size through reactive oxygen species signaling
Authors: Yamada Masashi , Han Xinwei , Benfey Philip. N.
Published: January 2018

Stem cell niche and root meristem size are maintained by intercellular interactions and signaling networks of a plant peptide hormone, Root Meristem Growth Factor 1 (RGF1). How RGF1 regulates root meristem development is an essential question to understand stem cell function. Although five receptors of RGF1 have recently been identified, the downstream signaling mechanism remains unknown. Here, we report a series of signaling events following RGF1 action. The RGF1-receptor pathway controls distribution of reactive oxygen species (ROS) along the developmental zones of the Arabidopsis root. We identify a novel transcription factor, RGF1 INDUCIBLE TRANSCRIPTION FACTOR 1 (RITF1), which plays a central role in mediating RGF1 signaling. Manipulating RITF1 expression leads to redistribution of ROS along the root developmental zones. Changes in ROS distribution, in turn, enhance the stability of the PLETHORA2 (PLT2) protein, a master regulator of root stem cells. Taken together, our study clearly depicts a signaling cascade initiated by RGF1 and links the RGF1 peptide to ROS regulatory mechanisms.
A Portable Structural Analysis Library for Reaction Networks
Authors: Bedaso Yosef , Bergmann Frank T. , Choi Kiri , Sauro Herbert M.
Published: January 2018

The topology of a reaction network can have a significant influence on the network’s dynamical properties. Such influences can include constraints on network flows and concentration changes or more insidiously result in the emergence of feedback loops. These effects are due entirely to mass constraints imposed by the network configuration and are important considerations before any dynamical analysis is made. Most established simulation software tools usually carry out some kind of structural analysis of a network before any attempt is made at dynamic simulation. In this paper we describe a portable software library,libStructural, that can carry out a variety of popular structural analyses that includes conservation analysis, flux dependency analysis and enumerating elementary modes. The library employs robust algorithms that allow it to be used on large networks with more than a two thousand nodes. The library accepts either a raw or fully labeled stoichiometry matrix or models written in SBML format. The software is written in standard C/C++ and comes with documentation and a test suite. The software is available for Windows, Mac OS X, and can be compiled easily on any Linux operating system. A language binding for Python is also available through the pip package manager making it trivial to install on any standard Python distribution. As a second example, we also create a newlibStructuralplugin for PathwayDesigner that allows solutions to be viewed graphically. The source code is licensed under the open source BSD license and is available on GitHub (https://github.com/sys-bio/Libstructural)
First spikes in visual cortex enable perceptual discrimination
Authors: Resulaj Arbora , Ruediger Sarah , Olsen Shawn R. , Scanziani Massimo
Published: January 2018

Visually guided perceptual decisions involve the sequential activation of a hierarchy of cortical areas. It has been hypothesized that a brief time window of activity in each area is sufficient to enable the decision but direct measurements of this time window are lacking. To address this question, we develop a visual discrimination task in mice that depends on visual cortex and in which we precisely control the time window of visual cortical activity as the animal performs the task at different levels of difficulty. We show that threshold duration of activity in visual cortex enabling perceptual discrimination is between 40 and 80 milliseconds. During this time window the vast majority of neurons discriminating the stimulus fire one or no spikes and less than 16% fire more than two. This result establishes that the firing of the first visually evoked spikes in visual cortex is sufficient to enable a perceptual decision.
Crystal structure of tribenzylbis(tetrahydrofuran-κO)lutetium(III)
Authors: Saliu Kuburat O. , Takats Josef , McDonald Robert
Published: January 2018

In the title compound, [Lu(C7H7)3(C4H8O)2] (1), the Lu ion is coordinated by three benzyl and two tetrahydrofuran ligands. Two of the benzyl groups are bonded in a classical η1-fashion through the methylene via the ipso-carbon atom of the benzyl ligand in addition to bonding through the methylene C atom, resulting in a modified trigonal–bipyramidal coordination geometry about the Lu center.
Further investigation on the nitration of BODIPY with cupric nitrate: crystal structures of 4,4-difluoro-1,3,5,7,8-pentamethyl-2-nitro-4-bora-3a,4a-diaza-s-indacene, 4,4-difluoro-3-nitro-8-phenyl-4-bora-3a,4a-diaza-s-indacene, and 3-chloro-6-ethyl-5,7,8-trimethyl-2-nitro-4,4-diphenyl-4-bora-3a,4a-diaza-s-indacene
Authors: Joshi Dhruval J. , Jun Meesook , Yang Lijing , Lough Alan J. , Yan Hongbin
Published: January 2018

The treatment of non-fully substituted 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) with cupric nitrate leads to the introduction of a nitro group at different positions of the BODIPY core, depending on the substitution pattern. This methodology complements the treatment of fully substituted BODIPY with cupric nitrate that was previously reported. The crystal structures of 4,4-difluoro-1,3,5,7,8-pentamethyl-2-nitro-4-bora-3a,4a-diaza-s-indacene, C14H16BF2N3O2 (5a) 4,4-difluoro-3-nitro-8-phenyl-4-bora-3a,4a-diaza-s-indacene, C15H10BF2N3O2
(5b) and 3-chloro-6-ethyl-5,7,8-trimethyl-2-nitro-4,4-diphenyl-4-bora-3a,4a-diaza-s-indacene, C26H25BClN3O2 (5d) are presented. In all three structures, the fused ring system is in a very flattened `V-shape', with dihedral angles between the two outer five membered rings of 8.12 (14), 6.67 (9) and 12.30 (18) Å for 5a, 5b and 5d, respectively. In each case, the central six-membered ring is in a flattened sofa conformation. In the crystal of 5a, molecules are linked by weak C—H...O and C—H...F hydrogen bonds forming sheets parallel to (10-1). In the crystal of 5b molecules are linked by weak C—H...O and C—H...F hydrogen bonds and π–π interactions forming sheets parallel to (001). In the crystal of 5d, weak C—H...O hydrogen bonds link molecules into chains along [001]. In compound 5d, the atoms of the nitro group were refined as disordered over two sets of sites with occupancies 0.618 (12) and 0.382 (12).
Crystal structure of the acyclic form of 1-deoxy-1-[(4-methoxyphenyl)(methyl)amino]-D-fructose
Authors: Mossine Valeri V. , Barnes Charles L. , Mawhinney Thomas P.
Published: January 2018

The title compound, C14H21NO6, (I), crystallizes exclusively in the acyclic keto form. In solution of (I), the acyclic tautomer represents only 10% of the population in equilibrium, with the other 90% consisting of β-pyranose, β-furanose, α-pyranose, and α-furanose cyclic forms. The carbohydrate chain in (I) has a zigzag conformation and the aromatic amine group has a transitional sp
2/sp
3 geometry. Bond lengths and valence angles in the carbohydrate portion compare well with the average values for related acyclic polyol structures. All of the hydroxyl groups are involved in intermolecular hydrogen bonding and form a two-dimensional network of infinite chains, which are interlinked by intramolecular hydrogen bonds and organized into R
8
8(16) homodromic ring patterns. A comparative Hirshfeld surfaces analysis of (I) and four other 1-amino-1-deoxy-D-fructose derivatives suggests the balance of hydrophilic/hydrophobic interactions plays a role in the crystal packing, favoring the acyclic isomer.
Crystal structure of ethyl 2-methyl-5,10-dioxo-4-phenyl-5,10-dihydro-4H-11-thia-1,4a-diazabenzo[b]fluorene-3-carboxylate
Authors: Yartsev Yegor , Lyubashov Pavel , Povstyanoy Vyacheslav , Povstyaniy Mykhailo , Lebedyeva Iryna
Published: January 2018

The title compound, C24H18N2O4S, crystallizes in the orthorhombic P212121 space group, indicating the existence of only one enantiomer with an S configuration of the chiral center in the crystal phase. The dihydropyrimidine ring adopts a twist-boat conformation while the quinone ring is slightly non-planar. In the crystal, molecules are linked by weak C—H...O and C—H...S hydrogen bonds and C—H...π interactions. In addition, a short intermolecular S...N contact of 3.250 (3) Å indicates an interaction between the S atom and the π-system of the thiazole ring.
Crystal structure of KNaCuP2O7, a new member of the diphosphate family
Authors: Fitouri Ines , Boughzala Habib
Published: January 2018

Potassium sodium copper(II) diphosphate(V), KNaCuP2O7, was synthesized by solid-state reactions. It crystallizes in the α-Na2CuP2O7 structure type in space group P21/n. In the crystal, CuO5 square-pyramids are linked to nearly eclipsed P2O7 groups by sharing corners to build up corrugated layers with composition [CuP2O7]2− that extend parallel to (010). The K+ and Na+ cations reside in the interlayer space and are connected to nine and seven O atoms, respectively. The structural model was validated by bond-valence-sum (BVS) and charge-distribution (CHARDI) analysis.
Binary and ternary charge-transfer complexes using 1,3,5-trinitrobenzene
Authors: Hill Tania , Levendis Demetrius C. , Lemmerer Andreas
Published: January 2018

Three binary and one ternary charge-transfer complexes have been made using 1,3,5-trinitrobenzene, viz. 1,3,5-trinitrobenzene–2-acetylnaphthalene (1/1), C6H3N3O6·C12H10O, (I), 1,3,5-trinitrobenzene–9-bromoanthracene (1/1), C14H9Br·C6H3N3O6, (II), 1,3,5-trinitrobenzene–methyl red (1/1), C15H15N3O2·C6H3N3O6, (III) (systematic name for methyl red: 2-{(E)-[4-(dimethylamino)phenyl]diazenyl}benzoic acid), and 1,3,5-trinitrobenzene–1-naphthoic acid–2-amino-5-nitropyridine (1/1/1), C6H3N3O6·C11H8O2·C5H5N3O2, (IV). All charge-transfer complexes show alternating donor and acceptor stacks, which have weak C—H...O hydrogen bonds perpendicular to the stacking axis. In addition, complex (IV) is a crystal engineering attempt to modify the packing of the stacks by inserting a third molecule into the structure. This third molecule is stabilized by strong hydrogen bonds between the carboxylic acid group of the donor molecule and the pyridine acceptor molecule.
3-Bromo-6-nitro-1-(prop-2-en-1-yl)-1H-indazole
Authors: Mohamed Abdelahi Mohamed Mokhtar , El Bakri Youness , Benchidmi Mohammed , Essassi El Mokhtar , Mague Joel T.
Published: January 2018

The asymmetric unit of the title compound, C10H8BrN3O2, contains two independent molecules differing primarily in the orientations of the allyl substituents [N—C—C=C torsion angles = −125.4 (16) and 116.0 (16)°]. The crystal packing involves slipped π–π stacking of indazole units, together with weak C—H...O and C—H...Br hydrogen bonds. The crystal studied was refined as a two-component twin.
(E)-5-{4-[2-(5-Ethylpyridin-2-yl)ethoxy]benzylidene}thiazolidine-2,4-dione
Authors: Balakumaran K. , Mosesbabu J. , Anireddy Jayashree , Chakkaravarthi G.
Published: January 2018

In the title compound, C19H18N2O3S, the thiazolidine ring makes dihedral angles of 46.97 (8) and 7.19 (9)° with the pyridine and benzene rings, respectively. The intramolecular structure is stabilized by a weak C—H...S hydrogen bond, which generates a S(6) graph-set motif, and a weak C—H...O contact. In the crystal, N—H...N and C—H...O hydrogen bonds leads to infinite one-dimensional chains along (201) and generate an R
2
2(7) ring-set motif. The crystal structure is further consolidated by weak π–π [centroid-to-centroid distance = 3.8204 (10) Å] interactions.
Ethyl (Z)-2-[2-(4-methylphenyl)hydrazin-1-ylidene]-3-oxo-3-(thiazol-2-ylamino)propanoate
Authors: El-Hiti Gamal A. , Mohamed Hanan A. , Abdel-Wahab Bakr F. , Alotaibi Mohammad Hayal , Hegazy Amany S. , Kariuki Benson M.
Published: January 2018

In the title compound, C15H16N4O3S, the dihedral angle between the aromatic rings is 15.90 (19)°. The molecule features two intramolecular N—H...O hydrogen bonds, which both close S(6) rings. In the crystal, weak C—H...O interactions link the molecules into [010] chains.
Impact of business model change on organizational success
Authors: Appelbaum Steven H. , Profka Edmiela , Depta Aleksandra Monika , Petrynski Bartosz
Published: January 2018

Purpose

The purpose of this paper is to investigate the impact of organizational change, more specifically business model change, on corporate employees’ motivation and, consequently, performance.

Design/methodology/approach

The main approaches and managerial frameworks on organization change implementation, as well as the assessment methods on whether the company is ready to implement the change, were identified by reviewing the current literature on the subject between 1940 and 2016.

Findings

Reviewed individual behavioral reactions and provided steps to encourage favorable individual employee perceptions.

Research limitations/implications

Existing gaps in supporting empirical data on the subject and a limited number of direct case studies and real-life scenarios. The research was primarily focused on employee motivation during the initial planning phase of organizational change, with lesser focus on motivation throughout and especially after the change process.

Practical implications

To benefit from the change, organizations must avoid improvising and should follow specific and formal change management procedures which take employee motivation and individual response towards change under consideration.

Social implications

By providing real-life illustrations of successful business model change implementations, current and future companies facing this type of change in the future can learn from these specific scenarios.

Originality/value

The distinction of business model change as a sub-type of organizational change and the study of employee motivation under a business model change specifically is the novel contribution of the paper.
House prices and neighbourhood amenities: beyond the norm?
Authors: McCord Michael James , Davis Peadar Thomas , Bidanset Paul , McCluskey William , McCord John , Haran Martin , MacIntyre Sean
Published: January 2018

Purpose

Understanding the key locational and neighbourhood determinants and their accessibility is a topic of great interest to policymakers, planners and property valuers. In Northern Ireland, the high level of market segregation means that it is problematic to understand the nature of the relationship between house prices and the accessibility to services and prominent neighbourhood landmarks and amenities. Therefore, this paper aims to quantify and measure the (dis)amenity effects on house pricing levels within particular geographic housing sub-markets.

Design/methodology/approach

Most hedonic models are estimated using regression techniques which produce one coefficient for the entirety of the pricing distribution, culminating in a single marginal implicit price. This paper uses a quantile regression (QR) approach that provides a “more complete” depiction of the marginal impacts for different quantiles of the price distribution using sales data obtained from 3,780 house sales transactions within the Belfast Housing market over 2014.

Findings

The findings emerging from this research demonstrate that housing and market characteristics are valued differently across the quantile values and that conditional quantiles are asymmetrical. Pertinently, the findings demonstrate that ordinary least squares (OLS) coefficient estimates have a tendency to over or under specify the marginal mean conditional pricing effects because of their inability to adequately capture and comprehend the complex spatial relationships which exist across the pricing distribution.

Originality value

Numerous studies have used OLS regression to measure the impact of key housing market externalities on house prices, providing a single estimate. This paper uses a QR approach to examine the impact of local amenities on house prices across the house price distribution.
Closing the strategy execution gap in the public sector
Authors: Olivier Anton Jacobus , Schwella Erwin
Published: January 2018

Purpose

In response to the significant gap between strategy planning and execution, a conceptual model was developed in an attempt to close this gap, particularly in the public sector. The paper aims to discuss this issue.

Design/methodology/approach

The paper is based on a literature review and participatory action research, stretching over ten case studies and eight years.

Findings

The MERIL-DE model integrates the identified “nine vital stratex components” of leadership, strategic planning, project management, alignment, MERIL (Measure, Evaluate, Report, Improve and Learn), drive, engagement, risk, and stakeholder management. The car analogy demonstrates this integration in a practical way.

Research limitations/implications

The conceptual model should be used as guide in the tailoring of a unique MERIL-DE model or Stratex Car for each public sector organization (PSO), according to its unique context.

Practical implications

In designing a tailored “Stratex Car” based on the MERIL-DE model, it is believed to close this gap significantly. The strategy execution framework is presented as a tool to assess the total strategy execution capacity (TSEC) of PSOs.

Originality/value

This is a new conceptual model for the unique public sector context, focusing on successful strategy execution in the public sector.
Assessing sustainability reports of US universities
Authors: Sassen Remmer , Azizi Leyla
Published: January 2018

Purpose

The purpose of this study is to assess sustainability reports of US universities to provide findings on the relative importance of disclosure topics.

Design/methodology/approach

The authors conducted content analysis by using a specific university-oriented catalogue of indicators to cover the specific sustainability-related aspects of this sector.

Findings

Sustainability reporting by universities is still in its early stages. The findings show a clear focus on the environmental dimension, whereas the university and the economic dimensions see lower levels of reporting. The social dimension is rarely addressed.

Research limitations/implications

Future research could use the results of this study as a basis for investigating stakeholder expectations towards universities’ sustainability reporting and developing university-specific sustainability reporting standards.

Practical implications

The results could be used to improve universities’ sustainability reporting, as “good” practices are now readily available.

Social implications

The level of reporting on the social dimension is very low. Therefore, developing political incentives to improve universities’ social performance might be of interest.

Originality/value

The investigated setting is unique and contributes several findings in a less-researched area along with several practical, social and research implications.