bluuebunny/crossref_metadata_2025 huggingface dataset:
A Propensity-Matched Analysis Between Standard Versus Tapered Oral Vancomycin Courses for the Management of Recurrent Clostridium difficile Infection
Authors: Gentry Chris A , Giancola Stephanie E , Thind Sharanjeet , Kurdgelashvili George , Skrepnek Grant H , Williams Riley J
Published: November 2017

Background

This study was conducted to compare clinical outcomes of oral vancomycin courses without taper versus oral vancomycin courses with taper for treatment of recurrent Clostridium difficile infection (CDI).

Methods

This investigation was a multicenter, retrospective, propensity score-matched analysis study using a Veterans Health Administration national clinical administrative database. Adult patients who were treated for recurrent CDI from any Veterans Affairs Medical Center between June 1, 2011 and October 31, 2016 were included if they were treated with oral vancomycin with or without a tapering regimen. The 2 groups were matched by next-nearest approach from a propensity score formula derived from independent variables associated with the selection of a taper regimen.

Results

Propensity score matching resulted in 2 well-matched groups consisting of 226 episodes of patients treated with a vancomycin taper regimen and 678 episodes treated by vancomycin regimen without taper. No difference was found for the primary outcome of 180-day recurrence (59 of 226 [26.1%] for taper regimens versus 161 of 678 [23.8%], P = .48). A secondary outcome of 90-day all-cause mortality met statistical significance, favoring a taper regimen (5.31% vs 9.29%, P = .049); however, secondary outcomes of 90-day recurrence and 180-day all-cause mortality were not different.

Conclusions

Vancomycin taper regimens did not provide benefit over vancomycin regimens without taper in preventing additional CDI recurrence in patients with first or second recurrent episodes in this propensity score-matched analysis.
Influence of Renal Function on Pharmacokinetics of Antiepileptic Drugs Metabolized by CYP3A4 in a Patient With Renal Impairment
Authors: Yamamoto Yoshiaki , Usui Naotaka , Nishida Takuji , Mori Miho , Takahashi Yukitoshi , Imai Katsumi , Kagawa Yoshiyuki , Inoue Yushi
Published: November 2017

Background:

Several studies have demonstrated that renal impairment not only decreases renal clearance but also hepatic clearance of medications that are CYP3A4 substrates. We evaluated the influence of renal function on the pharmacokinetics of antiepileptic drugs metabolized by CYP3A4.

Methods:

We retrospectively calculated the concentration/dose ratio (CD ratio) for topiramate and clobazam in an epilepsy patient with renal impairment. In addition, we determined the CD ratio of perampanel in 17 patients with normal renal function and compared it with that in the patient with renal impairment.

Results:

A patient with frontal lobe epilepsy and mild renal impairment [creatinine clearance (CCr): 67.7 mL/min] was taking phenytoin and 3 CYP3A4 substrates (topiramate, clobazam, and perampanel). With progression of renal impairment (CCr: 28.1 mL/min), the CD ratios of topiramate and clobazam increased by about 2-fold. The mean CD ratio of perampanel was 1740 ± 966 ng·mL−1·mg−1·kg−1 in the 17 patients with normal renal function using phenytoin. By contrast, the CD ratio of perampanel was markedly higher (range: 5327–9113 ng·mL−1·mg−1·kg−1) in the patient with renal impairment (CCr: <20 mL/min).

Conclusions:

These findings suggest that dose adjustment based on therapeutic drug monitoring is probably necessary when topiramate, clobazam, or perampanel is prescribed for patients with moderate-to-severe renal impairment.
The Optic Disc Drusen Studies Consortium Recommendations for Diagnosis of Optic Disc Drusen Using Optical Coherence Tomography
Authors: Malmqvist Lasse , Bursztyn Lulu , Costello Fiona , Digre Kathleen , Fraser J. Alexander , Fraser Clare , Katz Bradley , Lawlor Mitchell , Petzold Axel , Sibony Patrick , Warner Judith , Wegener Marianne , Wong Sui , Hamann Steffen
Published: November 2017

Background:

Making an accurate diagnosis of optic disc drusen (ODD) is important as part of the work-up for possible life-threatening optic disc edema. It also is important to follow the slowly progressive visual field defects many patients with ODD experience. The introduction of enhanced depth imaging optical coherence tomography (EDI-OCT) has improved the visualization of more deeply buried ODD. There is, however, no consensus regarding the diagnosis of ODD using OCT. The purpose of this study was to develop a consensus recommendation for diagnosing ODD using OCT.

Methods:

The members of the Optic Disc Drusen Studies (ODDS) Consortium are either fellowship trained neuro-ophthalmologists with an interest in ODD, or researchers with an interest in ODD. Four standardization steps were performed by the consortium members with a focus on both image acquisition and diagnosis of ODD.

Results:

Based on prior knowledge and experiences from the standardization steps, the ODDS Consortium reached a consensus regarding OCT acquisition and diagnosis of ODD. The recommendations from the ODDS Consortium include scanning protocol, data selection, data analysis, and nomenclature.

Conclusions:

The ODDS Consortium recommendations are important in the process of establishing a reliable and consistent diagnosis of ODD using OCT for both clinicians and researchers.
Endocarditis due to Rhodotorula mucilaginosa in a kidney transplanted patient: case report and review of medical literature
Authors: Cabral Andrea Maria , Siveira Rioja Suzimar da , Brito-Santos Fabio , Peres da Silva Juliana Ribeiro , MacDowell Maria Luíza , Melhem Marcia S. C. , Mattos-Guaraldi Ana Luíza , Hirata Junior Raphael , Damasco Paulo Vieira
Published: November 2017

Introduction. Endocarditis caused by yeasts is currently an emerging cause of infective endocarditis and, when accompanied byfever of unknown origin, is more severe since interferes with proper diagnosis and endocarditis treatment.

Case presentation. The Rio de Janeiro Infective Endocarditis Study Group reports a case of infectious endocarditis (IE) with negative blood cultures in a 45-year-old white female resident in Rio de Janeiro, Brazil, previously submitted to kidney transplantation. After diagnosis and intervention, the valve culture revealed Rhodotorula mucilaginosa. The clinical aspects and overview of endocarditis caused by Rhodotorula spp. demonstrated that R. muscilaginosa have been isolated from the last IE cases from kidney transplanted patients.

Conclusion. Though most of the patients (in literature) recovered well from endocarditis caused by Rhodotorula spp., physicians must be aware for diagnosis of fungemia and fungal treatment in kidney transplanted patients suffering of fever of unknown origin in the modern immunosuppressive treatment.
Proteome-wide analysis of phospho-regulated PDZ domain interactions through phosphomimetic proteomic peptide phage display
Authors: Sundell Gustav N. , Arnold Roland , Ali Muhammad , Orts Julien , Güntert Peter , Chi Celestine N. , Ivarsson Ylva
Published: November 2017

We report phosphomimetic proteomic peptide-phage display, a powerful large-scale method for finding ligands of short linear motif binding domains that simultaneously pinpoint functional Ser/Thr phosphosites in three steps. First, we computationally designed an oligonucleotide library encoding all human C-terminal peptides containing known or predicted Ser/Thr phosphosites and phosphomimetic variants thereof. Second, we incorporated these oligonucleotides into a phage library. Third, we screened the six PDZ (PSD-95/Dlg/ZO-1) domains of Scribble and DLG1 for binding and identified known and novel ligands from the human proteome, and whether these interactions may be regulated by ligand phosphorylation. We demonstrate that the Scribble PDZ domains preferentially bind to ligands with phosphomimetic mutations at two distinct positions, and show that the equilibrium dissociation constant for Scribble PDZ1 with the C-terminal peptide of RPS6KA2 is enhanced over four-fold by phosphorylation. We elucidate the molecular determinants of phosphopeptide binding through NMR structure determination and mutational analysis. Finally, we discuss the role of Ser/Thr phosphorylation as a switching mechanism of PDZ domain interactions.
Voltage-dependent inward currents in smooth muscle cells of skeletal muscle arterioles
Authors: Ulyanova Alexandra V. , Shirokov Roman E.
Published: November 2017

Voltage-dependent inward currents responsible for the depolarizing phase of action potentials were characterized in smooth muscle cells of 4thorder arterioles in mouse skeletal muscle. Currents through L-type Ca2+channels were expected to be dominant; however, action potentials were not eliminated in nominally Ca2+-free bathing solution or by addition of L-type Ca2+channel blocker nifedipine (10 μM). Instead, Na+channel blocker tetrodotoxin (TTX, 1 μM) reduced the maximal velocity of the upstroke at low, but not at normal (2 mM), Ca2+in the bath. The magnitude of TTX-sensitive currents recorded with 140 mM Na+was about 20 pA/pF. TTX-sensitive currents decreased five-fold when Ca2+increased from 2 to 10 mM. The currents reduced three-fold in the presence of 10 mM caffeine, but remained unaltered by 1 mM of isobutylmethylxanthine (IBMX). In addition to L-type Ca2+currents (15 pA/pF in 20 mM Ca2+), we also found Ca2+currents that are resistant to 10 μM nifedipine (5 pA/pF in 20 mM Ca2+). Based on their biophysical properties, these Ca2+currents are likely to be through voltage-gated T-type Ca2+channels. Our results suggest that Na+and at least two types (T- and L-) of Ca2+voltage-gated channels contribute to depolarization of smooth muscle cells in skeletal muscle arterioles. Voltage-gated Na+channels appear to be under a tight control by Ca2+signaling.
Within-infection diversity ofPlasmodium falciparumantigens reflects host-mediated selection
Authors: Early Angela M. , Lievens Marc , MacInnis Bronwyn , Ockenhouse Christian F. , Volkman Sarah K. ,   RTS,S Clinical Trial Partnership Committee of Investigators,, Wirth Dyann F. , Neafsey Daniel E.
Published: November 2017

Host immunity exerts strong selection on pathogens, but it does not act in a uniform manner across individual hosts. By providing a direct approach for understanding host-specific selection pressures, patterns of intra-host pathogen diversity complement population genetic analyses performed on broad geographic scales. Here, we perform a combined analysis of inter- and intra-host diversity for the malaria parasitePlasmodium falciparumwith haplotype sequences of three antigens sampled from over 4,500 natural infections in sub-Saharan Africa using targeted deep sequencing. We find that multi-strain infections in young children contain non-random combinations of parasite genotypes, and identify individual amino acid positions that may contribute to strain-specific blocking of infections. These results demonstrate for the first time that natural host defenses toPlasmodiumdetectably impact which infections proceed to the blood stage within a given host. This selection partially explains the extreme amino acid diversity observed at many parasite antigens and suggests that vaccines targeting such proteins should account for the impact of allele-specific immunity.
Scalable Bayesian inference for high-dimensional neural receptive fields
Authors: Aoi Mikio C. , Pillow Jonathan W.
Published: November 2017

We examine the problem of rapidly and efficiently estimating a neuron’s linear receptive field (RF) from responses to high-dimensional stimuli. This problem poses important statistical and computational challenges. Statistical challenges arise from the need for strong regularization when using correlated stimuli in high-dimensional parameter spaces, while computational challenges arise from extensive time and memory costs associated with evidence-optimization and inference in high-dimensional settings. Here we focus on novel methods for scaling up automatic smoothness determination (ASD), an empirical Bayesian method for RF estimation, to high-dimensional settings. First, we show that using a zero-padded Fourier domain representation and a “coarse-to-fine” evidence optimization strategy gives substantial improvements in speed and memory, while maintaining exact numerical accuracy. We then introduce a suite of scalable approximate methods that exploit Kronecker and Toeplitz structure in the stimulus autocovariance, which can be related to the method of expected log-likelihoods [1]. When applied together, these methods reduce the cost of estimating an RF with tensor order D and d coefficients per tensor dimension from O(d3D) time and O(d2D) space for standard ASD to O(Dd log d) time and O(Dd) space. We show that evidence optimization for a linear RF with 160K coefficients using 5K samples of data can be carried out on a laptop in < 2s.
Clingen Cancer Somatic Working Group – standardizing and democratizing access to cancer molecular diagnostic data to drive translational research
Authors: Madhavan Subha , Ritter Deborah , Micheel Christine , Rao Shruti , Roy Angshumoy , Sonkin Dmitriy , Mccoy Matthew , Griffith Malachi , Griffith Obi L , Mcgarvey Peter , Kulkarni Shashikant ,   On Behalf Of The Clingen Somatic Working Group
Published: November 2017

A growing number of academic and community clinics are conducting genomic testing to inform treatment decisions for cancer patients (1). In the last 3–5 years, there has been a rapid increase in clinical use of next generation sequencing (NGS) based cancer molecular diagnostic (MolDx) testing (2). The increasing availability and decreasing cost of tumor genomic profiling means that physicians can now make treatment decisions armed with patient-specific genetic information. Accumulating research in the cancer biology field indicates that there is significant potential to improve cancer patient outcomes by effectively leveraging this rich source of genomic data in treatment planning (3). To achieve truly personalized medicine in oncology, it is critical to catalog cancer sequence variants from MolDx testing for their clinical relevance along with treatment information and patient outcomes, and to do so in a way that supports large-scale data aggregation and new hypothesis generation. One critical challenge to encoding variant data is adopting a standard of annotation of those variants that are clinically actionable. Through the NIH-funded Clinical Genome Resource (ClinGen) (4), in collaboration with NLM’s ClinVar database and >50 academic and industry based cancer research organizations, we developed the Minimal Variant Level Data (MVLD) framework to standardize reporting and interpretation of drug associated alterations (5). We are currently involved in collaborative efforts to align the MVLD framework with parallel, complementary sequence variants interpretation clinical guidelines from the Association of Molecular Pathologists (AMP) for clinical labs (6). In order to truly democratize access to MolDx data for care and research needs, these standards must be harmonized to support sharing of clinical cancer variants. Here we describe the processes and methods developed within the ClinGen’s Somatic WG in collaboration with over 60 cancer care and research organizations as well as CLIA-certified, CAP-accredited clinical testing labs to develop standards for cancer variant interpretation and sharing.
A simulation and comparison of dynamic functional connectivity methods
Authors: Thompson William Hedley , Richter Craig Geoffrey , Plavén-Sigray Pontus , Fransson Peter
Published: November 2017

There is a current interest in quantifying brain dynamic functional connectivity (DFC) based on neuroimaging data such as fMRI. Many methods have been proposed, and are being applied, revealing new insight into the brain’s dynamics. However, given that the ground truth for DFC in the brain is unknown, many concerns remain regarding the accuracy of proposed estimates. Since there exists many DFC methods it is difficult to assess differences in dynamic brain connectivity between studies. Here, we evaluate five different methods that together represent a wide spectrum of current approaches to estimating DFC (sliding window, tapered sliding window, temporal derivative, spatial distance and jackknife correlation). In particular, we were interested in each methods’ ability to track changes in covariance over time, which is a key property in DFC analysis. We found that all tested methods correlated positively with each other, but there were large differences in the strength of the correlations between methods. To facilitate comparisons with future DFC methods, we propose that the described simulations can act as benchmark tests for evaluation of methods. In this paper, we present dfcbenchmarker, which is a Python package where researchers can easily submit and compare their own DFC methods to evaluate its performance.
Effects of mutating α-tubulin lysine 40 on sensory dendrite development
Authors: Jenkins Brian V. , Saunders Harriet A. J. , Record Helena L. , Johnson-Schlitz Dena M. , Wildonger Jill
Published: November 2017

Microtubules are essential to neuronal structure and function. Axonal and dendritic microtubules are enriched in post-translational modifications that impact microtubule dynamics, transport, and microtubule-associated proteins. Acetylation of α-tubulin lysine 40 (K40) is a prominent, conserved modification of neuronal microtubules. However, the cellular role of microtubule acetylation remains controversial. To resolve how microtubule acetylation might affect neuronal morphogenesis we mutated endogenous α-tubulin in vivo using a new fly strain that facilitates the rapid knock-in of designerα-tubulinalleles. Leveraging our new strain, we found that microtubule acetylation, as well as polyglutamylation and (de)tyrosination, is not essential for survival. However, we found that dendrite branch refinement in sensory neurons relies on α-tubulin K40. Mutagenesis of K40 reveals moderate yet significant changes in dendritic lysosome transport, microtubule polymerization, and Futsch distribution in dendrites but not axons. Our studies point to an unappreciated role for α-tubulin K40 and acetylation in dendrite morphogenesis. While our results are consistent with the idea that microtubule acetylation patterns microtubule function within neurons, they also suggest there may be a structural requirement for α-tubulin K40.

Summary Statement

Neurons are enriched in post-translationally modified microtubules. Targeted mutagenesis of endogenous α-tubulin in flies reveals that dendrite branch refinement is altered by acetylation-blocking mutations.
Genetic variation across the human olfactory receptor repertoire alters odor perception
Authors: Trimmer Casey , Keller Andreas , Murphy Nicolle R. , Snyder Lindsey L. , Willer Jason R. , Nagai Maira , Katsanis Nicholas , Vosshall Leslie B. , Matsunami Hiroaki , Mainland Joel D.
Published: November 2017

The human olfactory receptor repertoire is characterized by an abundance of genetic variation that affects receptor response, but the perceptual effects of this variation are unclear. To address this issue, we sequenced the OR repertoire in 332 individuals and examined the relationship between genetic variation and 276 olfactory phenotypes, including the perceived intensity and pleasantness of 68 odorants at two concentrations, detection thresholds of three odorants, and general olfactory acuity. Genetic variation in a single OR frequently associated with odorant perception, and we validated 10 cases in which in vitro OR function correlated with in vivo odorant perception using a functional assay. This more than doubles the published examples of this phenomenon. For eight of these 10 cases, reduced receptor function associated with reduced intensity perception. In addition, we used participant genotypes to quantify genetic ancestry and found that, in combination with single OR genotype, age and gender, we can explain between 10 and 20% of the perceptual variation in 15 olfactory phenotypes, highlighting the importance of single OR genotype, ancestry, and demographic factors in variation of olfactory perception.
Variation in traction forces during cell cycle progression
Authors: Vianay Benoit , Senger Fabrice , Alamos Simon , Anjur-Dietrich Maya , Bearce Elizabeth , Cheeseman Bevan , Lee Lisa , Théry Manuel
Published: November 2017

Tissue morphogenesis results from the interplay between cell growth and mechanical forces. While the impact of forces on cell proliferation has been fairly well characterized, the inverse relationship is much less understood. Here we investigated how traction forces vary during cell cycle progression. Cell shape was constrained on micropatterned substrates in order to distinguish variations in cell contractility from cell size increase. We performed traction force measurements of asynchronously dividing cells expressing a cell-cycle reporter, to obtain measurements of contractile forces generated during cell division. We found that forces tend to increase as cells progress through G1, before reaching a plateau in S phase, and then decline during G2. This biphasic behaviour revealed a previously undocumented specific and opposite regulation of cell contractility during each cell cycle stage.
Context of Psychotropic Drug Delivery Modulates its Neurobehavioral Effects: the Case of Methylphenidate
Authors: Sar-El Roy , Raz Gal , Lubianiker Nitzan , Sharon Haggai , Hendler Talma
Published: November 2017

Pharmacotherapy is substantially hindered by poor drug targeting, resulting in low specificity and efficacy. Here, we tested a novel, non-invasive targeting approach (termed functional-pharmacology), which couples drug administration with a task that activates the drug’s sites-of-action in the brain, thus possibly improving absorption and efficacy. Methylphenidate (MPH) or Placebo were administered to healthy subjects, which then performed a cognitive induction or a control task. N-Back fMRI before and after drug-task coupling measured therapeutic effects. Only following MPH, subjects that performed better in the cognitive induction task showed greater improvements in N-back performance. Moreover, only under MPH-Cognitive induction condition, there existed a significant correlation between improved recruitment of N-Back rDLPFC activation, and a concurrent improvement in task performance. Importantly, mediation analysis suggested a causal role of rDLPFC activation in these coupling effects. Our results support the functional-pharmacology concept feasibility and efficacy, hence opening a new horizon for patient-tailored, context-driven drug therapy.
Evaluation of protein-ligand docking methods on peptide-ligand complexes for docking small ligands to peptides
Authors: Singh Sandeep , Srivastava Hemant Kumar , Kishor Gaurav , Singh Harinder , Agrawal Piyush , Raghava G.P.S.
Published: November 2017

In the past, many benchmarking studies have been performed on protein-protein and protein-ligand docking however there is no study on peptide-ligand docking. In this study, we evaluated the performance of seven widely used docking methods (AutoDock, AutoDock Vina, DOCK 6, PLANTS, rDock, GEMDOCK and GOLD) on a dataset of 57 peptide-ligand complexes. Though these methods have been developed for docking ligands to proteins but we evaluate their ability to dock ligands to peptides. First, we compared TOP docking pose of these methods with original complex and achieved average RMSD from 4.74Å for AutoDock to 12.63Å for GEMDOCK. Next we evaluated BEST docking pose of these methods and achieved average RMSD from 3.82Å for AutoDock to 10.83Å for rDock. It has been observed that ranking of docking poses by these methods is not suitable for peptide-ligand docking as performance of their TOP pose is much inferior to their BEST pose. AutoDock clearly shows better performance compared to the other six docking methods based on their TOP docking poses. On the other hand, difference in performance of different docking methods (AutoDock, AutoDock Vina, PLANTS and DOCK 6) was marginal when evaluation was based on their BEST docking pose. Similar trend has been observed when performance is measured in terms of success rate at different cut-off values. In order to facilitate scientific community a web server PLDbench has been developed (http://webs.iiitd.edu.in/raghava/pldbench/).
Perturbed Mitochondrial Metabolism in Islets from Donors with Type-2 Diabetes
Authors: Sun Jiangming , Jain Ruchi , Andersson Lotta E. , Medina Anya , Storm Petter , Spégel Peter , Mulder Hindrik
Published: November 2017

There is a preponderance for genes involved in ß-cell function among gene variants associated with future risk of type-2 diabetes (T2D). ß-cell function is controlled by metabolism of glucose, yielding signals triggering and amplifying insulin secretion. Perturbed ß-cell metabolism is a likely, albeit not proven, cause of T2D. We profiled metabolites in islets from T2D and non-diabetic donors, and found altered levels of mitochondrial metabolites in T2D. Analysis of genes encoding proteins localized to mitochondria (MitoCarta) by RNA-seq in an extended sample of islets revealed genes whose expression was associated with glycaemia- and/or BMI. Expression of two of these, α-methylacyl-CoA racemase(AMACR)and methylmalonyl-CoA mutase(MUT),was influenced by genetic variation (cis-eQTL). Silencing ofAMACRandMUTin insulin-secreting cells reduced hormone secretion by 40-50%. In conclusion, by linking the metabolome to the transcriptome, we showed that perturbed mitochondrial metabolism is a feature of ß-cell dysfunction in T2D.

[Supplementary material is available for this article.]
The effect of offspring number on the adaptation speed of a polygenic trait
Authors: Pfenninger Markus
Published: November 2017

There is increasing evidence that rapid phenotypic adaptation of quantitative traits is not uncommon in nature. However, the circumstances under which rapid adaptation of polygenic traits occurs are not yet understood. Building on previous concepts of soft selection, i.e. frequency and density dependent selection, I developed and tested the hypothesis that adaptation speed of a polygenic trait depends on the number of offspring per breeding pair in a randomly mating diploid population. Using individual based modelling on a range of offspring per parent (2-200) in populations of various size (100-10000 individuals), I could show that the by far largest proportion of variance (42%) was explained by the offspring number, regardless of genetic trait architecture (10-50 loci, different locus contribution distributions). In addition, it was possible to identify the majority of the responsible loci and account for even more of the observed phenotypic change with a moderate population size. The simulation results suggest that offspring numbers may a crucial factor for the adaptation speed of quantitative loci. Moreover, as large offspring numbers translates to a large phenotypic variance in the offspring of each parental pair, this genetic bet hedging strategy increases the chance to contribute to the next generation in unpredictable environments.
Duplication and divergence of Sox genes in spiders
Authors: Paese Christian L. B. , Leite Daniel J. , Schoenauer Anna , McGregor Alistair P. , Russell Steven
Published: November 2017

Background

The Sox family of transcription factors are present and conserved in the genomes of all metazoans examined to data and are known to play important developmental roles in vertebrates and insects. However, outside the commonly studiedDrosophilamodel little is known about the extent or conservation of the Sox family in other arthropod species. Here we characterise the Sox family in two chelicerate species, the spidersParasteatoda tepidariorumandStegodyphus mimosarum, which have experienced a whole genome duplication (WGD) in their evolutionary history.

Results

We find that virtually all of the duplicate Sox genes have been retained in these spiders after the WGD. Analysis of the expression of Sox genes inP. tepidariorumembryos indicates that it is likely that some of these genes have neofunctionalised after duplication. Our expression analysis also strengthens the view that an orthologue of vertebrate Group B1 genes,SoxNeuro, is implicated in the earliest events of CNS specification in both vertebrates and invertebrates. In addition, a gene in theDichaete/Sox21bclass is dynamically expressed in the spider segment addition zone, suggestive of an ancient regulatory mechanism controlling arthropod segmentation as recently suggested for flies and beetles. Together with the recent analysis of Sox gene expression in the embryos of other arthropods, our findings are also indicative of conserved functions for some of these genes, including a role forSoxCandSoxDgenes in CNS development,SoxFin limb development and a tantalising suggestion thatSoxEgenes may be involved in gonadogenesis across the metazoa.

Conclusions

Our study provides a new chelicerate perspective to understanding the evolution and function of Sox genes and how the retention of duplicates of such important tool-box genes after WGD has contributed to different aspects of spider embryogenesis. Future characterisation of the function of these genes in spiders will help us to better understand the evolution of the regulation of important developmental processes in arthropods and other metazoans including neurogenesis and segmentation.
Enhanced JBrowse plugins for epigenomics data visualization
Authors: Hofmeister Brigitte T. , Schmitz Robert J.
Published: November 2017

New sequencing techniques require new visualization strategies, as is the case for epigenomics data such as DNA base modifications, small non-coding RNAs, and histone modifications. We present a set of plugins for the genome browser JBrowse that are targeted for epigenomics visualizations. Specifically, we have focused on visualizing DNA base modifications, small non-coding RNAs, stranded read coverage, and sequence motif density. Additionally, we present several plugins for improved user experience such as configurable, high-quality screenshots. In visualizing epigenomics with traditional genomics data, we see these plugins improving scientific communication and leading to discoveries within the field of epigenomics.
Coordination between discrete Mitotic Arrest Deficient 1 (MAD1) domains is required for efficient mitotic checkpoint signaling
Authors: Ji Wenbin , Luo Yibo , Ahmad Ejaz , Liu Song-Tao
Published: November 2017

As a sensitive signaling system, the mitotic checkpoint ensures faithful chromosome segregation by delaying anaphase onset when even a single kinetochore is unattached. The key signal amplification reaction for the checkpoint is the conformational conversion of open MAD2 (O-MAD2) into closed MAD2 (C-MAD2). The reaction was suggested to be catalyzed by an unusual catalyst, a MAD1:C-MAD2 tetramer, but how the catalysis is executed and regulated remains elusive. Here we report that in addition to the well-characterized middle region (MIM), both amino- and carboxyl-terminal domains (NTD and CTD) of MAD1 also contribute to the mitotic checkpoint. In contrast to MIM that stably associates with C-MAD2, MAD1-NTD and CTD surprisingly bind to both O-MAD2 and C-MAD2, suggesting their interactions with substrates and products of the O-C conversion. MAD1-NTD also interacts with CTD. MPS1 kinase interacts with and phosphorylates both NTD and CTD. The phosphorylation reduces the NTD:CTD interaction and CTD interaction with MPS1. Mutating CTD phosphorylation sites including Thr716 compromises MAD2 binding and the checkpoint responses. Ser610 and Tyr634 also contribute to the checkpoint. Our results have uncovered previously unknown interactions of MAD1-NTD and CTD with MAD2 conformers and their regulation by MPS1 kinase, providing novel insights into the mitotic checkpoint signaling.
An automated statistical technique for counting distinct multiple sclerosis lesions can recover aspects of lesion history and provide relevant disease information
Authors: Dworkin Jordan D. , Linn Kristin A. , Oguz Ipek , Fleishman Greg M. , Bakshi Rohit , Nair Govind , Calabresi Peter A. , Henry Roland G. , Oh Jiwon , Papinutto Nico , Pelletier Daniel , Rooney William , Stern William , Sicotte Nancy L. , Reich Daniel S. , Shinohara Russell T. ,   the NAIMS Cooperative
Published: November 2017

Background

Lesion load is a common biomarker in multiple sclerosis, yet it has historically shown modest associations with clinical outcomes. Lesion count, which encapsulates the natural history of lesion formation and is thought to provide complementary information, is difficult to assess in patients with confluent (i.e. spatially overlapping) lesions. We introduce a statistical technique for cross-sectionally counting pathologically distinct lesions.

Methods

MRI is used to assess the probability of lesion at each location. The texture of this map is quantified using a novel technique, and clusters resembling the center of a lesion are counted.

Results

Validity was demonstrated by comparing the proposed count to a gold-standard count in 60 subjects observed longitudinally. The counts were highly correlated (r = .97, p < .001) and not significantly different (t59 = −0.83, p > .40). Reliability was determined using 14 scans of a clinically stable subject acquired at 7 sites, and variability of lesion count was equivalent to that of lesion load. Accounting for lesion load and age, lesion count was negatively associated (t58 = −2.73, p < .01) with the Expanded Disability Status Scale (EDSS). Average lesion size had a higher association with EDSS (r =.35, p < .01) than lesion load (r = .10, p > .40) or lesion count (r = −.12, p > .30) alone.

Conclusion

These findings demonstrate that it is possible to recover important aspects of the natural history of lesion formation without longitudinal data, and suggest that lesion size provides complementary information about disease.

Grant Support

The project described was supported in part by the NIH grants R01 NS085211, R21 NS093349, and R01 NS094456 from the National Institute of Neurological Disorders and Stroke (NINDS). The study was also supported by the Intramural Research Program of NINDS and the Race to Erase MS Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.
Gene network analysis identifies a central post-transcriptional regulator of cellular stress survival
Authors: Tien Matthew Z. , Fiebig Aretha , Crosson Sean
Published: November 2017

Cells adapt to shifts in their environment by remodeling transcription. Measuring changes in transcription at the genome scale is now routine, but defining the functional significance of individual genes within large gene expression datasets remains a major challenge. We applied a network-based algorithm to interrogate publicly available transcription data to predict genes that serve major functional roles inCaulobacter crescentusstress survival. This approach identified GsrN, a conserved small RNA that is directly controlled by the general stress sigma factor, στ, and functions as a potent post-transcriptional regulator of survival under multiple stress conditions. GsrN expression is both necessary and sufficient to protect cells from hydrogen peroxide, where it functions by base pairing with the leader ofkatGmRNA and promoting catalase/peroxidase expression. We conclude that GsrN convenes a post-transcriptional layer of gene expression that serves a central functional role in stress physiology.
WISP3 mutation associated with pseudorheumatoid dysplasia
Authors: Sailani M. Reza , Chappell James , Jingga Inlora , Narasimha Anil , Zia Amin , Lynch Janet Linnea , Mazrouei Safoura , Bernstein Jonathan A. , Aryani Omid , Snyder Michael P.
Published: November 2017

Progressive pseudorheumatoid dysplasia (PPD) is a skeletal dysplasia characterized by predominant involvement of articular cartilage with progressive joint stiffness. Here we report genetic characterization of a consanguineous family segregating an uncharacterized from of skeletal dysplasia. Whole-exome sequencing of four affected siblings and their parents identified a loss-of-function homozygous mutation in the WISP3 gene, leading to diagnosis of PPD in the affected individuals. The identified variant (Chr6: 112382301; WISP3:c.156C>A p.Cys52*) is rare and predicted to cause premature termination of the WISP3 protein.
“Corps” leadership: a cadet perspective on shared leadership
Authors: Martin Ira H. , Prophet Trevor , Owens Christopher , Martin JennyMae , Plummer Gabe
Published: November 2017

Purpose

The purpose of this paper is to enhance understanding of shared leadership in a military academy setting.

Design/methodology/approach

A qualitative methodology was selected to ask senior cadets about a shared leadership concept at the United States Coast Guard Academy, known as the “corps leading the corps.” Cadets responded to, “what does the corps leading the corps mean to you?” via a paper and pencil survey. Cadet responses were coded using content analysis.

Findings

Three higher-order dimensions emerged from the data: autonomy and empowerment, developing self and others, and role modeling.

Originality/value

The paper provides emerging leaders’ commentary to incorporating a shared leadership concept within an educational environment.
Mother-child disagreements on child anxiety: associated factors
Authors: Giuseppone Kathryn R. , Brumariu Laura E.
Published: November 2017

Purpose

Previous literature demonstrated low-to-moderate rates of agreement between children and mothers regarding child anxiety. The purpose of this paper is to evaluate factors related to differences between mother-child dyads who disagreed vs agreed in their reports of child anxiety symptoms.

Design/methodology/approach

In total, 87 children aged 9-12 years old and their mothers completed questionnaires regarding maternal perceptions of child behavior, maternal separation anxiety about the child’s individuation, and mother-child relationship characteristics.

Findings

The results showed that mothers in mother-child dyads who disagreed on child anxiety symptoms, compared to those in dyads who agreed on child anxiety symptoms, perceived their children as showing higher affect intensity and behavioral problems. They also expressed greater anxiety about the children’s individuation process, characterized in part by children’s increased autonomy and decline of reliance on them. Further, children in dyads who disagreed, compared to those in dyads who agreed, reported lower mother-child attachment security.

Originality/value

The results extend the literature by identifying specific factors related to the discrepancy between mothers’ and children’s reports of childhood anxiety in early adolescence. The results highlight the need to consider both mothers’ and children’s views when assessing childhood anxiety. Importantly, the results also indicate that specific factors investigated in this study, including maternal perception of children’s behavioral problems and their affect intensity, maternal anxiety about child individuation, and mother-child attachment security, could be used to inform clinical decisions regarding informant discrepancies.
The tattoo as a document
Authors: Sundberg Kristina , Kjellman Ulrika
Published: November 2017

Purpose

The purpose of this paper is to investigate how tattoos can be considered documents of an individual’s identity, experiences, status and actions in a given context, relating to ideas stating that archival records/documents can be of many types and have different functions. The paper also wants to discuss how tattoos serve as a bank of memories and evidence on a living body; in this respect, the tattooed body can be viewed as an archive, which immortalises and symbolises the events and relationships an individual has experienced in his or her life, and this in relation to a specific social and cultural context.

Design/methodology/approach

To discuss these issues, the authors take the point of departure in the tattoo practice of Russian/Soviet prisoners. The tattoo material referred to is from the “Russian Criminal Tattoo Archive”. The archive is created by FUEL Design and Publishing that holds the meanings of the tattoos as explained inRussian Criminal Tattoo Encyclopaedia Volume I-III. The authors exemplify this practice with two photographs of Soviet/Russian prisoners and their tattoos. By using a semiotic analysis that contextualises these images primarily through literature studies, the authors try to say something about what meaning these tattoos might carry.

Findings

The paper argues that it is possible to view the tattoo as a document, bound to an individual, reflecting his/her life and a given social and cultural context. As documents, they provide the individual with the essential evidence of his or her endeavours in a criminal environment. They also function as an individual’s memory of events and relationships (hardships and comradeships). Subsequently, the tattoos help create and sustain an identity. Finally, the tattoo presents itself as a document that may represent a critique of a dominant society or simply the voice of the alienated.

Originality/value

By showing how tattoos can be seen as documents and memory records, this paper brings a new kind of item into information and archival studies. It also uses theories and concepts from information and archival studies to put new light on the functions of tattoos.
The “digital divide” for rural small businesses
Authors: Richmond William , Rader Scott , Lanier Clinton
Published: November 2017

Purpose

This research aims to contribute to the marketing and entrepreneurship literature by showing that there is a new, different digital divide for rural small businesses based not on access to the internet but on its use for digital marketing.

Design/methodology/approach

This research uses data from the state of North Carolina, examining 1,000 businesses across both rural and non-rural geographies in terms of their deployment of Web and social media marketing technologies. Further, within the rural category, analysis proceeded to ascertain potential differences between “western” (mountainous) and “eastern” (coastal) rural areas.

Findings

The research concludes that despite significant improvements in broadband access in rural areas, rural small businesses still lagged in terms of adoption of state-of-the-art Web and social media marketing practices. However, between western and eastern rural areas, differences in this lag in best practice were not discovered.

Research limitations/implications

Although the data collected were limited to small businesses in North Carolina, the results may not generalize all small businesses.

Originality/value

While underserved, rural economies received apt attention with regard to closing the proverbial “digital divide” in terms of broadband (high-speed internet) services. Resolution of this disparity does not necessarily portend that those same constituents also closed the gap in terms of using online, marketing best practices that are facilitated by broadband. Policymakers wishing to promote rural economies need to address not only the existence of an internet infrastructure but also the small businesses’ willingness and ability to use it effectively.
Money or mind? What matters most in influencing low-income earners to be energy efficient?
Authors: Russell-Bennett Rebekah , Mulcahy Rory , Little Jo-Anne , Swinton Tim
Published: November 2017

Purpose

Designing a social marketing intervention for low-income earners requires an understanding of the key motivations. As part of the Low-Income Earner Energy Efficiency Programme, this study investigates the key factors that influence energy behaviours amongst Australian young low-income earners as part of the Reduce Your Juice social marketing programme. The authors also investigate the effect of gender.

Design/methodology/approach

An online survey of 753 low-income renters was conducted using validated measures. The data were analysed using structural equation modelling.

Findings

The two factors that had the highest influence on intentions for energy-saving behaviours was the “mind” factor of self-efficacy and “money” factor of price concern. There were gender differences in the effect of bill control and price concern on intentions for different energy efficiency behaviours.

Practical implications

This study provides guidance on the factors to emphasise when designing an energy efficiency programme for low-income earners.

Social implications

This study provides evidence for different motivations amongst low-income earners for energy efficiency programmes and that a “one size fits all” approach may not be effective.

Originality/value

While there is high interest in the public sector for motivating young-adult low-income earners to change their energy behaviours, little is known about the key factors that motivate intentions to engage in these behaviours.
A prospective cause of death classification system for maternal deaths in low and middle‐income countries: results from the Global Network Maternal Newborn Health Registry
Authors: Pasha O , McClure EM , Saleem S , Tikmani SS , Lokangaka A , Tshefu A , Bose CL , Bauserman M , Mwenechanya M , Chomba E , Carlo WA , Garces AL , Figueroa L , Hambidge KM , Krebs NF , Goudar S , Kodkany BS , Dhaded S , Derman RJ , Patel A , Hibberd PL , Esamai F , Tenge C , Liechty EA , Moore JL , Wallace DD , Koso‐Thomas M , Miodovnik M , Goldenberg RL
Published: November 2017

Objective

To describe the causes of maternal death in a population‐based cohort in six low‐ and middle‐income countries using a standardised, hierarchical, algorithmic cause of death (COD) methodology.

Design

A population‐based, prospective observational study.

Setting

Seven sites in six low‐ to middle‐income countries including the Democratic Republic of the Congo (DRC), Guatemala, India (two sites), Kenya, Pakistan and Zambia.

Population

All deaths among pregnant women resident in the study sites from 2014 to December 2016.

Methods

For women who died, we used a standardised questionnaire to collect clinical data regarding maternal conditions present during pregnancy and delivery. These data were analysed using a computer‐based algorithm to assign cause of maternal death based on the International Classification of Disease—Maternal Mortality system (trauma, termination of pregnancy‐related, eclampsia, haemorrhage, pregnancy‐related infection and medical conditions). We also compared the COD results to healthcare‐provider‐assigned maternal COD.

Main outcome measures

Assigned causes of maternal mortality.

Results

Among 158 205 women, there were 221 maternal deaths. The most common algorithm‐assigned maternal COD were obstetric haemorrhage (38.6%), pregnancy‐related infection (26.4%) and pre‐eclampsia/eclampsia (18.2%). Agreement between algorithm‐assigned COD and COD assigned by healthcare providers ranged from 75% for haemorrhage to 25% for medical causes coincident to pregnancy.

Conclusions

The major maternal COD in the Global Network sites were haemorrhage, pregnancy‐related infection and pre‐eclampsia/eclampsia. This system could allow public health programmes in low‐ and middle‐income countries to generate transparent and comparable data for maternal COD across time or regions.

Tweetable abstract

An algorithmic system for determining maternal cause of death in low‐resource settings is described.