bluuebunny/crossref_metadata_2025 huggingface dataset:
Histologic Features of Gastrointestinal Tract Biopsies in IgA Vasculitis (Henoch-Schönlein Purpura)
Authors: Louie Christine Y. , Gomez Adam J. , Sibley Richard K. , Bass Dorsey , Longacre Teri A.
Published: February 2018

Immunoglobulin A (IgA) vasculitis or Henoch-Schönlein purpura (HSP) typically occurs in the pediatric population, although rare cases also occur in adults. Gastrointestinal (GI) involvement is common. The “classic” histologic finding in IgA vasculitis (HSP) is leukocytoclastic vasculitis (LCV); other histologic features in biopsies of IgA vasculitis (HSP) have only been rarely described. The pathology archival files at our institution were searched for GI biopsies from patients with IgA vasculitis (HSP). Slides were retrieved and histologic and clinical features were reviewed. We identified 16 patients with IgA vasculitis (HSP) with a GI biopsy series, including both adult and pediatric patients. The most common histologic abnormality was lamina propria hemorrhage (all cases) with many cases also showing lamina propria fibrin deposition with red cell sludging and nuclear debris (7 cases). Twelve of the 16 duodenal biopsies had acute duodenitis; 3 of which were severe and erosive. Several also had an eosinophilic infiltrate. Seven of the 9 jejunal and/or ileal biopsies had acute jejunitis or ileitis. An acute colitis or proctitis was observed in 9/12 colorectal biopsies. Four biopsies contained LCV; in each of these cases, the involved vessels were small capillaries within the lamina propria. Only 1 biopsy contained deeper submucosal vessels, but they were uninvolved. Sites involved by LCV included the colorectum (2 cases), colorectum and terminal ileum, terminal ileum only, duodenum, and jejunum (1 case each). All patients presented with abdominal pain; 13/16 developed a rash, 1 following the index biopsy. Other presenting symptoms included diarrhea and/or hematochezia (8 cases), nausea/vomiting (5 cases), and intussusception (1 case). Four patients had concurrent skin biopsies showing LCV; only 1 of these patients had LCV on GI biopsy. Indications for biopsy included nonspecific presenting symptoms, absence of rash at presentation, and/or failure to respond adequately to steroid therapy. Biopsies are commonly performed in patients with or without suspected IgA vasculitis (HSP) to rule out infection, inflammatory bowel disease, and less commonly, vasculitis. In general, vasculitis is not commonly observed in GI biopsies of patients with IgA vasculitis (HSP), and the spectrum of findings includes neutrophilic infiltrate within the small bowel and colon, with the duodenum most commonly affected. While the clinical and histologic findings may mimic early inflammatory bowel disease, the presence of predominant small bowel involvement, especially erosive duodenitis, should raise suspicion for IgA vasculitis (HSP). Biopsies should be obtained before steroid therapy is initiated, if possible.
An Unusual Complication of Bone Wax Utilization
Authors: Fahradyan Artur , Ohanisian Levonti , Tsuha Michaela , Park Matthew J. , Hammoudeh Jeffrey A.
Published: February 2018

Bone wax is a commonly used hemostatic agent with minimal complications. Some of the known complications include inflammation, granuloma formation, infection, and impaired osteogenesis. Several clinical reports of bone wax migration have also been reported. In this paper, the authors present a rare patient of bone wax migration intracranially in a 6-year-old patient who initially underwent craniotomy for the evacuation of subdural hematoma and repair of depressed skull fracture. The patient then underwent craniotomy scalp scar revision several months later. Postoperatively he developed short-term memory loss, apraxia, and word finding difficulties. The imaging findings were consistent with the presence of a foreign body centered in the posterior aspect of the left middle temporal gyrus, which was surgically removed and found to be bone wax. The patient recovered well with complete improvement of his neurologic symptoms.
New Ways of “Seeing” the Mechanistic Heterogeneity of Multiple Sclerosis Plaque Pathogenesis
Authors: Meltzer Ethan I. , Costello Fiona E. , Frohman Elliot M. , Frohman Teresa C.
Published: February 2018

Background:

Over the past few decades, we have witnessed a transformation with respect to the principles and pathobiological underpinnings of multiple sclerosis (MS). From the traditional rubric of MS as an inflammatory and demyelinating disorder restricted to central nervous system (CNS) white matter, our contemporary view has evolved to encompass a broader understanding of the variable mechanisms that contribute to tissue injury, in a disorder now recognized to affect white and grey matter compartments.

Evidence Acquisition:

A constellation of inflammation, ion channel derangements, bioenergetic supply: demand mismatches within the intra-axonal compartment, and alterations in the dynamics and oximetry of blood flow in CNS tissue compartments are observed in MS. These findings have raised questions regarding how histopathologic heterogeneity may influence the diverse clinical spectrum of MS; and, accordingly, how individual treatment needs vary from 1 patient to the next.

Results:

We are now on new scaffolding in MS; one that promises to translate key clinical and laboratory observations to the application of emerging patient-centered therapies.

Conclusions:

This review highlights our current knowledge of the underlying disease mechanisms in MS, explores the inflammatory and neurodegenerative consequences of tissue damage, and examines physiologic factors that contribute to bioenergetic homeostasis within the CNS of affected patients.
Effect of Fascia Penetration on Sensory Nerve Conduction in the Superficial Radial Nerve
Authors: Park Hye Jung , Yoon Joon Shik , Rhee Won Ihl , Kim Jea Won , Yang Seung Nam , Won Sun Jae
Published: February 2018

Purpose:

The aim of this study was to identify the effects of fascia penetration on superficial radial sensory nerve action potential amplitude.

Methods:

The penetration point (PP) at which the nerve penetrated the brachioradialis fascia and became superficial was observed using ultrasonography. The sensory nerve action potential amplitude was measured at five points: the penetration point, 2 and 4 cm proximal to the PP, and 2 and 4 cm distal to the PP.

Results:

The sensory nerve action potential amplitude at the penetration point and at 2 and 4 cm distal to the PP was significantly larger than that at 2 and 4 cm proximal to the PP. The largest amplitude was obtained 2 cm distal to the PP.

Conclusions:

The sensory nerve action potential of the superficial radial nerve changes significantly around the fascia penetration point.
Cost-effectiveness of a Ceramide-Infused Skin Barrier Versus a Standard Barrier
Authors: Berger Ariel , Inglese Gary , Skountrianos George , Karlsmark Tonny , Oguz Mustafa
Published: February 2018

PURPOSE:

To assess the cost-effectiveness of a ceramide-infused skin barrier (CIB) versus other skin barriers (standard of care) among patients who have undergone ostomy creation.

DESIGN:

Cost-effectiveness analysis, based on a decision-analytic model that was estimated using data from the ADVOCATE (A Study Determining Variances in Ostomy Skin Conditions And The Economic Impact) trial, which investigated stoma-related healthcare costs over 12 weeks among patients who recently underwent fecal ostomy, and from other sources.

SUBJECTS AND SETTING:

Analysis was based on a hypothetical cohort of 1000 patients who recently underwent fecal ostomy; over a 1-year period, 500 patients were assumed to use CIB and 500 were assumed to use standard of care.

METHODS:

We adapted a previous economic model to estimate expected 1-year costs and outcomes among persons with a new ostomy assumed to use CIB versus standard of care. Outcomes of interest included peristomal skin complications (PSCs) (up to 2 during the 1-year period of interest) and quality-adjusted life days (QALDs); QALDs vary from 1, indicating a day of perfect health to 0, indicating a day with the lowest possible health (deceased). Subjects were assigned QALDs on a daily basis, with the value of the QALD on any given day based on whether the patient was experiencing a PSC. Costs included those related to skin barriers, ostomy accessories, and care of PSCs. The incremental cost-effectiveness of CIB versus standard of care was estimated as the incremental cost per PSC averted and QALD gained, respectively; net monetary benefit of CIB was also estimated. All analyses were run using the perspective of an Australian payer.

RESULTS:

On a per-patient basis, use of CIB was expected over a 1-year period to result in 0.16 fewer PSCs, an additional 0.35 QALDs, and a savings of A$180 (Australian dollars, US $137) in healthcare costs all versus standard of care. Management with CIB provided a net monetary benefit (calculated as the product of maximum willingness to pay for 1 QALD times additional QALDs with CIB less the incremental cost of CIB) of A$228 (US $174). Probabilistic sensitivity analysis was also completed; it revealed that 97% of model runs resulted in fewer expected PSCs with CIB; 92% of these runs resulted in lower expected costs with CIB.

CONCLUSIONS:

Findings suggest that the CIB is a cost-effective skin barrier for persons living with an ostomy.
Estimating sleep parameters using an accelerometer without sleep diary
Authors: van Hees V.T. , Sabia S. , Jones S.E. , Wood A.R. , Anderson K.N. , Kivimäki M. , Frayling T.M. , Pack A. I. , Bucan M , Trenell M.I. , Mazzotti Diego R. , Gehrman P. R. , Singh-Manoux B. A. , Weedon M. N.
Published: February 2018

Wrist worn raw-data accelerometers are used increasingly in large scale population research. We examined whether sleep parameters can be estimated from these data in the absence of sleep diaries. Our heuristic algorithm uses the variance in estimated z-axis angle and makes basic assumptions about sleep interruptions. Detected sleep period time window (SPT-window), was compared against sleep diary in 3752 participants (range=60-82years) and polysomnography in sleep clinic patients (N=28) and in healthy good sleepers (N=22). The SPT-window derived from the algorithm was 10.9 and 2.9 minutes longer compared with sleep diary in men and women, respectively. Mean C-statistic to detect the SPT-window compared to polysomnography was 0.86 and 0.83 in clinic-based and healthy sleepers, respectively. We demonstrated the accuracy of our algorithm to detect the SPT-window. The value of this algorithm lies in studies such as UK Biobank where a sleep diary was not used.
Quantitative understanding of molecular competition as a hidden layer of gene regulatory network
Authors: Yuan Ye , Wei Lei , Hu Tao , Li Shuailin , Cheng Tianrun , Lei Jinzhi , Xie Zhen , Zhang Michael Q. , Wang Xiaowo
Published: February 2018

Molecular competition is ubiquitous, essential and multifunctional throughout diverse biological processes. Competition brings about trade-offs of shared limited resources among the cellular components, and it thus introduce a hidden layer of regulatory mechanism by connecting components even without direct physical interactions. By abstracting the analogous competition mechanism behind diverse molecular systems, we built a unified coarse-grained competition motif model to systematically compare experimental evidences in these processes and analyzed general properties shared behind them. We could predict in what molecular environments competition would reveal threshold behavior or display a negative linear dependence. We quantified how competition can shape regulator-target dose-response curve, modulate dynamic response speed, control target expression noise, and introduce correlated fluctuations between targets. This work uncovered the complexity and generality of molecular competition effect, which might act as a hidden regulatory mechanism with multiple functions throughout biological networks in both natural and synthetic systems.
Analysis of global and site-specific radiation damage in cryo-EM
Authors: Hattne Johan , Shi Dan , Glynn Calina , Zee Chih-Te , Gallagher-Jones Marcus , Martynowycz Michael W. , Rodriguez Jose A. , Gonen Tamir
Published: February 2018

Micro-crystal electron diffraction (MicroED) is an emerging method in cryo-EM for structure determination using nanocrystals. It has been used to solve structures of a diverse set of biomolecules and materials, in some cases to sub-atomic resolution. However, little is known about the damaging effects of the electron beam on samples during such measurements. We assess global and site-specific damage from electron radiation on nanocrystals of proteinase K and of a prion hepta-peptide and find that the dynamics of electron-induced damage follow well-established trends observed in X-ray crystallography. Metal ions are perturbed, disulfide bonds are broken, and acidic side chains are decarboxylated while the diffracted intensities decay exponentially with increasing exposure. A better understanding of radiation damage in MicroED improves our assessment and processing of all types of cryo-EM data.
Dissection of the microProtein miP1 floral repressor complex in Arabidopsis
Authors: Rodrigues Vandasue L. , Dolde Ulla , Straub Daniel , Eguen Tenai , Botterweg-Paredes Esther , Sun Bin , Hong Shinyoung , Graeff Moritz , Li Man-Wah , Gendron Joshua M. , Wenkel Stephan
Published: February 2018

MicroProteins have emerged as potent regulators of transcription factor activity. Here we use a combination of forward genetics and proteomics to dissect the miP1a/b microProtein complex that acts to delay the floral transition in Arabidopsis. The microProteins miP1a and miP1b can bridge an interaction between the flowering promoting factor CONSTANS (CO) and the TOPLESS (TPL) co-repressor protein to represses flowering. We find that the JUMONJI14 (JMJ14) histone demethylase is part of this repressor complex that can initiate chromatin changes in FLOWERING LOCUS T (FT) gene, the direct target of CO. Plants with mutations in JMJ14 exhibit an early flowering phenotype that is largely dependent on the activity of CO, supporting a role for CO in this repressive complex. When mis-expressed at the shoot apex, CO can induce early flowering only in the jmj14 background. Our results indicate that the repressor acts in the shoot apical meristem to keep it in an undifferentiated state until the leaf-derived florigen signal induces the conversion into a floral meristem.
Identification of candidate genes for gelatinization temperature, gel consistency and pericarp color by GWAS in rice based on SLAF-sequencing
Authors: Yang Xinghai , Xia Xiuzhong , Zeng Yu , Nong Baoxuan , Zhang Zongqiong , Wu Yanyan , Xiong Faqian , Zhang Yuexiong , Liang Haifu , Deng Guofu , Li Danting
Published: February 2018

Rice is an important cereal in the world, uncovering the genetic basis of agronomic traits in rice landraces genes associated with agronomically important traits is indispensable for both understanding the genetic basis of phenotypic variation and efficient crop improvement. Gelatinization temperature, gel consistency and pericarp color are important indices of rice cooking and eating quality evaluation and potential nutritional importance, which attract wide attentions in the application of genetic and breeding. To dissect the genetic basis of gelatinization temperature (GT), gel consistency (GC) and pericarp color (PC), a total of 419 rice landraces core germplasm collections consisting of 330indicalines, 78japonicalines and 11 uncertain varieties were grown, collected, then GT, GC, PC were measured for two years, and sequenced using Specific Locus Amplified Fragment Sequencing (SLAF) technology. In this study, 261,385,070 clean reads and 56,768 polymorphic SLAF tags were obtained, which a total of 211,818 single nucleotide polymorphisms (SNPs) were discovered. With 208,993 SNPs meeting the criterion of minor allele frequency (MAF) > 0.05 and integrity> 0.5, the phylogenetic tree and population structure analysis were performed for all 419 rice landraces, and the whole panel mainly separated into six subpopulations based on population structure analysis. Genome-wide association study (GWAS) was carried out for the whole panel,indicasubpanel andjaponicasubpanel with subset SNPs respectively. One quantitative trait locus (QTL) on chromosome 6 for GT was detected in the whole panel andindicasubpanel, and one QTL associated with GC was located on chromosome 6 in the whole panel andindicasubpanel. For the PC trait, 8 QTLs were detected in the whole panel on chromosome 1, 3, 4, 7, 8, 10 and 11, and 7 QTLs in theindicasubpanel on chromosome 3, 4, 7, 8, 10 and 11. The loci on chromosome 3, 8, 10 and 11 have not been identified previously, and they may be the candidate genes of pericarp color. For the three traits, no QTL was detected injaponicasubpanel probably because of the polymorphism repartition between the subpanel, or small population size ofjaponicasubpanel. This paper provides new gene resources and insights into the molecular mechanisms of important agricultural trait of rice phenotypic variation and genetic improvement of rice quality variety breeding.
Differences in firing efficiency, chromatin and transcription underlie the developmental plasticity of the Arabidopsis originome
Authors: Sequeira-Mendes J. , Vergara Z. , Peiró R. , Morata J. , Aragüez I. , Costas C. , Mendez-Giraldez R. , Casacuberta J.M. , Bastolla U. , Gutierrez C.
Published: February 2018

Eukaryotic genome replication depends on thousands of DNA replication origins (ORIs) that constitute the originome. A major challenge is to learn ORI biology in multicellular organisms in the context of growing organs to understand their developmental plasticity. We have determined the originome and chromatin landscape of Arabidopsis thaliana at two stages of postembryonic development. ORIs associate with multiple chromatin signatures including TSS but also regulatory regions and heterochromatin, where ORIs colocalize with retrotransposons. In addition, quantitative analysis of ORI activity led us to conclude that strong ORIs have high GC content and clusters of GGN trinucleotides. Development primarily influences ORI firing strength rather than ORI location. ORIs that preferentially fire at early developmental stages colocalize with GC-rich heterochromatin whereas at later stages with transcribed genes, perhaps as a consequence of changes in chromatin features associated with developmental processes. Our study provides the originome of an organism at the postembryo stage that should allow us to study ORI biology in response to development, environment and mutations with a quantitative approach. In a wider scope, the computational strategies developed here can be transferred to other eukaryotic systems.
Evidence for genetic correlations and bidirectional, causal effects between smoking and sleep behaviours
Authors: Gibson Mark , Munafò Marcus R , Taylor Amy E , Treur Jorien L.
Published: February 2018

Introduction

Cigarette smokers are at increased risk of poor sleep behaviours. However, it is largely unknown whether these associations are due to shared (genetic) risk factors and/or causal effects (which may be bi-directional).

Methods

We obtained summary-level data of genome-wide association studies of smoking (smoking initiation (n=74,035), cigarettes per day (n=38,181) and smoking cessation (n=41,278)) and sleep behaviours (sleep duration and chronotype, or ‘morningness’) (n=128,266) and insomnia (n=113,006)). Using LD score regression, we calculated genetic correlations between smoking and sleep behaviours. To investigate causal effects, we employed Mendelian randomization (MR), both with summary-level data and individual level data (n=333,581 UK Biobank participants). For MR with summary-level data, individual genetic variants were combined with inverse-variance weighted meta-analysis, weighted median regression and MR Egger regression methods.

Results

We found positive genetic correlations between insomnia and smoking initiation (rg=0.27, 95% CI 0.06 to 0.49) and insomnia and cigarettes per day (rg=0.15, 0.01 to 0.28), and negative genetic correlations between sleep duration and smoking initiation (rg=-0.14, -0.26 to -0.01) and chronotype and smoking cessation (rg=-0.18, -0.31 to -0.06). MR analyses provided strong evidence that smoking more cigarettes per day causally decreases the odds of being a morning person, and weak evidence that insomnia causally increases smoking heaviness and decreases smoking cessation odds.

Conclusions

Smoking and sleep behaviours show moderate genetic correlation. Heavier smoking seems to causally affect circadian rhythm and there is some indication that insomnia increases smoking heaviness and hampers cessation. Our findings point to sleep as a potentially interesting smoking treatment target.
Hybridization and rampant mitochondrial introgression among fire salamanders in peninsular Italy
Authors: Bisconti Roberta , Porretta Daniele , Arduino Paola , Nascetti Giuseppe , Canestrelli Daniele
Published: February 2018

Discordance between mitochondrial and nuclear patterns of population genetic structure is providing key insights into the eco-evolutionary dynamics between and within species, and their assessment is highly relevant to biodiversity monitoring practices based on DNA barcoding approaches. Here, we investigate the population genetic structure of the fire salamanderSalamandra salamandrain peninsular Italy. Both mitochondrial and nuclear markers clearly identified two main population groups. However, nuclear and mitochondrial zones of geographic transition between groups were located 600 km from one another. The overall pattern of genetic variation, together with morphological and fossil data, suggest that a rampant mitochondrial introgression triggered the observed mitonuclear discordance, following a post-glacial secondary contact between lineages. Moreover, at a shallower level of population structure, we observed evidence of asymmetric introgression of nuclear genes between two sub-groups in southern Italy. Our results clearly show the major role played by reticulate evolution in shaping the structure ofSalamandra salamandrapopulations and, together with similar findings in other regions of the species’ range, contribute to identify the fire salamander as a particularly intriguing case to investigate the complexity of mechanisms triggering patterns of mitonuclear discordance in animals.
Perceived timing of active head movement at different speeds
Authors: Sachgau Carolin , Chung William , Barnett-Cowan Michael
Published: February 2018

The central nervous system must determine which sensory events occur at the same time. Actively moving the head corresponds with large changes in the relationship between the observer and the environment, sensorimotor processing, and spatiotemporal perception. Numerous studies have shown that head movement onset must precede the onset of other sensory events in order to be perceived as simultaneous, indicating that head movement perception is slow. Active head movement perception has been shown to be slower than passive head movement perception and dependent on head movement velocity, where participants who move their head faster than other participants require the head to move even earlier than comparison stimuli to be perceived as simultaneous. These results suggest that head movement perception is slower (i.e., suppressed) when the head moves faster. The present study used a within-subjects design to measure the point of subjective simultaneity (PSS) between active head movement speeds and a comparison sound stimulus. Our results clearly show that i) head movement perception is faster when the head moves faster within-subjects, ii) active head movement onset must still precede the onset of other sensory events (Average PSS: -123 to -52 ms) in order to be perceived as occurring simultaneously even at the fastest speeds (Average peak velocity: 76°/s to 257°/s). We conclude that head movement perception is slow, but that this delay is minimized with increased speed. While we do not provide evidence against sensory suppression, which requires active versus passive head movement comparison, our results do rule out velocity-based suppression.
Impaired Spatial Reorientation in the 3xTg-AD Mouse Model of Alzheimer’s Disease
Authors: Stimmell Alina C. , Baglietto-Vargas David , Moseley Shawn C. , Lapointe Valérie , Thompson Lauren M. , LaFerla Frank M. , McNaughton Bruce L. , Wilber Aaron A.
Published: February 2018

In early Alzheimer’s disease (AD) spatial navigation is impaired; however, the precise cause of this impairment is unclear. Recent evidence suggests that getting lost in new surroundings is one of the first impairments to emerge in AD. It is possible that getting lost in new surroundings represents a failure to use distal cues to get oriented in space. Therefore, we set out to look for impaired use of distal cues for spatial orientation in a mouse model of amyloidosis (3xTg-AD). To do this, we trained mice to shuttle to the end of a track and back to an enclosed start box to receive a water reward. Then, mice were trained to stop in an unmarked reward zone to receive a brain stimulation reward. The time required to remain in the zone for a reward was increased across training, and the track was positioned in a random start location for each trial. We found that 6-month female, but not male, 3xTg-AD mice were impaired. Male and female mice had only intracellular pathology and male mice had less pathology, particularly in the dorsal hippocampus. Thus, AD may cause spatial disorientation as a result of impaired use of landmarks.
Titer estimation for quality control (TEQC) method: a practical approach for optimal production of protein complexes using the baculovirus expression vector system
Authors: Imasaki Tsuyoshi , Wenzel Sabine , Yamada Kentaro , Bryant Megan L. , Takagi Yuichiro
Published: February 2018

The baculovirus expression vector system (BEVS) is becoming the method of choice for expression of many eukaryotic proteins and protein complexes for biochemical, structural and pharmaceutical studies. Significant technological advancement has made generation of recombinant baculoviruses easy, efficient and user-friendly. However, there is a tremendous variability in the amount of proteins made using the BEVS, including different batches of virus made to express the same proteins. Yet, what influences the overall production of proteins or protein complexes remains largely unclear. Many downstream applications, particularly protein structure determination, require purification of large quantities of proteins in a repetitive manner, calling for a reliable experimental set-up to obtain the protein or protein complexes of interest consistently. During our investigation of optimizing the expression of the Mediator Head module, we discovered that the ‘initial infectivity’ was an excellent indicator of overall production of protein complexes. Further, we show that this initial infectivity can be mathematically described as a function of multiplicity of infection (MOI), correlating recombinant protein yield and virus titer. All these findings led us to develop the Titer Estimation for Quality Control (TEQC) method, which enables researchers to estimate initial infectivity, titer/MOI values in a simple and affordable way, and to use these values to quantitatively optimize protein expressions utilizing BEVS in a highly reproducible fashion.
Sequencing Metrics of Human Genomes Extracted from Single Cancer Cells Individually Isolated in a Valveless Microfluidic Device
Authors: Marie Rodolphe , Pødenphant Marie , Koprowska Kamila , Bærlocher Loic , Vulders Roland C.M. , Wilding Jennifer , Ashley Neil , McGowan Simon J. , van Strijp Dianne , van Hemert Freek , Olesen Tom , Agersnap Niels , Bilenberg Brian , Sabatel Celine , Schira Julien , Kristensen Anders , Bodmer Walter , van der Zaag Pieter J. , Mir Kalim U.
Published: February 2018

Sequencing the genomes of individual cells enables the direct determination of genetic heterogeneity amongst cells within a population. We have developed an injection-moulded valveless microfluidic device in which single cells from colorectal cell (LS174T, LS180 and RKO) lines and fresh colorectal cancers are individually trapped, their genomes extracted and prepared for sequencing, using multiple displacement amplification (MDA). Ninety nine percent of the DNA sequences obtained mapped to a reference human genome, indicating that there was effectively no contamination of these samples from non-human sources. In addition, most of the reads are correctly paired, with a low percentage of singletons (0.17 ± 0.06 %) and we obtain genome coverages approaching 90%. To achieve this high quality, our device design and process shows that amplification can be conducted in microliter volumes as long as extraction is in sub-nanoliter volumes. Our data also demonstrates that high quality single cell sequencing can be achieved using a relatively simple, inexpensive and scalable device.
Shugoshin is essential for meiotic prophase checkpoints inC. elegans
Authors: Bohr Tisha , Nelson Christian R. , Giacopazzi Stefani , Lamelza Piero , Bhalla Needhi
Published: February 2018

The conserved factor Shugoshin is dispensable inC. elegansfor the two-step loss of sister chromatid cohesion that directs the proper segregation of meiotic chromosomes. We show that theC. elegansortholog of Shugoshin, SGO-1, is required for checkpoint activity in meiotic prophase. This role in checkpoint function is similar to that of the meiotic chromosomal protein, HTP-3. Nullsgo-1mutants exhibit additional phenotypes similar to that of a partial loss of function allele of HTP-3: premature synaptonemal complex disassembly, the activation of alternate DNA repair pathways and an inability to recruit a conserved effector of the DNA damage pathway, HUS-1. SGO-1 localizes to pre-meiotic nuclei, when HTP-3 is present but not yet loaded onto chromosome axes, suggesting an early role in regulating meiotic chromosome metabolism. We propose that SGO-1 acts during pre-meiotic replication to ensure fully functional meiotic chromosome architecture, rendering these chromosomes competent for checkpoint activity and normal progression of meiotic recombination. Given that most research on Shugoshin has been focused on its regulation of sister chromatid cohesion in meiosis, this novel role may be conserved but previously uncharacterized in other organisms. Further, our findings expand the repertoire of Shugoshin’s functions beyond coordinating regulatory activities at the centromere.
Insights into Parkinson’s disease from computational models of the basal ganglia
Authors: Humphries Mark D. , Obeso Jose , Dreyer Jakob Kisbye
Published: February 2018

Movement disorders arise from the complex interplay of multiple changes to neural circuits. Successful treatments for these disorders could interact with these complex changes in myriad ways, and as a consequence their mechanisms of action and their amelioration of symptoms are incompletely understood. Using Parkinson’s disease as a case-study, we review here how computational models are a crucial tool for taming this complexity, across causative mechanisms, consequent neural dynamics, and treatments. For mechanisms, we review models that capture the effects of losing dopamine on basal ganglia function; for dynamics, we discuss models that have transformed our understanding of how beta-band (15-30 Hz) oscillations arise in the parkinsonian basal ganglia. For treatments, we touch on the breadth of computational modelling work trying to understand the therapeutic actions of deep brain stimulation. Collectively, models from across all levels of description are providing a compelling account of the causes, symptoms, and treatments for Parkinson’s disease.
TheAquilegiagenome: adaptive radiation and an extraordinarily polymorphic chromosome with a unique history
Authors: Filiault Danièle , Ballerini Evangeline S. , Mandáková Terezie , Aköz Gökçe , Derieg Nathan , Schmutz Jeremy , Jenkins Jerry , Grimwood Jane , Shu Shengqiang , Hayes Richard D. , Hellsten Uffe , Barry Kerrie , Yan Juying , Mihaltcheva Sirma , Karafiátová Miroslava , Nizhynska Viktoria , Lysak Martin A. , Hodges Scott A. , Nordborg Magnus
Published: February 2018

The columbine genusAquilegiais a classic example of an adaptive radiation, involving a wide variety of pollinators and habitats. Here we present the genome assembly ofA. coerulea‘Goldsmith’, complemented by high-coverage sequencing data from 10 wild species covering the world-wide distribution. Our analyses reveal extensive allele sharing among species and demonstrate that introgression and selection played a role in theAquilegiaradiation. We also present the remarkable discovery that the evolutionary history of an entire chromosome differs from that of the rest of the genome – a phenomenon which we do not fully understand, but which highlights the need to consider chromosomes in an evolutionary context.
Transition State Characteristics During Cell Differentiation
Authors: Brackston Rowan D. , Lakatos Eszter , Stumpf Michael P.H.
Published: February 2018

Models describing the process of stem-cell differentiation are plentiful, and may offer insights into the underlying mechanisms and experimentally observed behaviour. Waddington’s epigenetic landscape has been providing a conceptual framework for differentiation processes since its inception. It also allows, however, for detailed mathematical and quantitative analyses, as the landscape can, at least in principle, be related to mathematical models of dynamical systems. Here we focus on a set of dynamical systems features that are intimately linked to cell differentiation, by considering exemplar dynamical models that capture important aspects of stem cell differentiation dynamics. These models allow us to map the paths that cells take through gene expression space as they move from one fate to another, e.g. from a stem-cell to a more specialized cell type. Our analysis highlights the role of the transition state (TS) that separates distinct cell fates, and how the nature of the TS changes as the underlying landscape changes— change that can be induced by e.g. cellular signalling. We demonstrate that models for stem cell differentiation may be interpreted in terms of either a static or transitory landscape. For the static case the TS represents a particular transcriptional profile that all cells approach during differentiation. Alternatively, the TS may refer to the commonly observed period of heterogeneity as cells undergo stochastic transitions.
“Light-box” accelerated growth of poinsettias: LED-only Illumination
Authors: Weerasuriya Charitha , Detez Stewart , Hock Ng Soon , Hughes Andrew , Callaway Michael , Harrison Iain , Katkus Tomas , Juodkazis Saulius
Published: February 2018

For the current commercialized agricultural industry which requires a reduced product lead time to customer and supply all year round, an artificial light emitting diode (LED)-based illumination has high potential due to high efficiency of electrical-to-light conversion. The main advantage of the deployed Red Green Blue Amber LED lighting system is colour mixing capability, which means the ability to generate all the colours in the spectrum by using three or four primary colour LEDs. The accelerated plant growth was carried out in a “light-box” which was made to generate an artificial day/night cycle and had a capability to tune the colour mixing ratio along the colour temperature curve of the chromaticity diagram. The control group of plants form the same initial batch was grown on the same shelf in a greenhouse at the same conditions with addition of artificial illumination by incandescent lamps for few hours. More dense and better quality (hence, commercial value) plants were grown in the light-box. Costs and efficiency projections of LED lamps for horticultural applications is discussed together with required capital investment. The total cost of the “light-box” including LED lamps and electronics was 850 AUD.
Torso-like is a component of the hemolymph and regulates the insulin signalling pathway in Drosophila
Authors: Henstridge Michelle A. , Aulsebrook Lucinda , Koyama Takashi , Johnson Travis K. , Whisstock James C. , Tiganis Tony , Mirth Christen K. , Warr Coral G.
Published: February 2018

In Drosophila key developmental transitions are governed by the steroid hormone ecdysone. A number of neuropeptide-activated signalling pathways control ecdysone production in response to environmental signals, including the insulin signalling pathway, which regulates ecdysone production in response to nutrition. Here, we find that the Membrane Attack Complex/Perforin-like protein Torso-like, best characterised for its role in activating the Torso receptor tyrosine kinase in early embryo patterning, also regulates the insulin signalling pathway in Drosophila. We previously reported that the small body size and developmental delay phenotypes of torso-like null mutants resemble those observed when insulin signalling is reduced. Here we report that, in addition to growth defects, torso-like mutants also display metabolic and nutritional plasticity phenotypes characteristic of mutants with impaired insulin signalling. We further find that in the absence of torso-like the expression of insulin-like peptides is increased, as is their accumulation in the insulin-producing cells. Finally, we show that Torso-like is a component of the hemolymph and that it is required in the prothoracic gland to control developmental timing and body size. Taken together, our data suggest that the secretion of Torso-like from the prothoracic gland influences the activity of insulin signalling throughout the body in Drosophila.

ARTICLE SUMMARY

In many animals distinct developmental transitions are crucial for the coordinated progression from the juvenile stage to adulthood. In Drosophila, the transition from an immature larva into a reproductively mature adult is controlled by the steroid hormone ecdysone. Several neuropeptide-activated signalling pathways, including the insulin signalling pathway, regulate ecdysone production in response to environmental cues. Here we find that the perforin-like protein Torso-like regulates the insulin signalling pathway. We show that Torso-like is secreted into circulation where it acts to influence insulin-like peptide activity, revealing a novel mechanism for the regulation of insulin signalling in Drosophila.
ssRNA/DNA-Sensors via Embedded Strand-Displacement Programs in CRISPR/Cas9 Guides
Authors: Jakimo Noah , Chatterjee Pranam , Jacobson Joseph M
Published: February 2018

RNA and DNA profiles can help classify a variety of biological states, including disease, metabolism and cell type. In a proof-of-concept study on novel genetically encodable components for detecting single-stranded oligonucleotides, we engineered switchable CRISPR guide RNA (swigRNA) with Cas9 affinity that is conditional on sensing an oligo trigger molecule (trigRNA or trigDNA). RNA- and DNA-sensing swigRNAs that serve as off-to-on and on-to-off switches for Cas9 cleavage were achieved by computational design of hybridization dependencies in the guide. This study highlights functional swigRNA structures that implement toehold-gated strand-displacement with their triggers, and should merit further engineering and kinetic characterization.
Heterochromatin Interactions Maintain Homologous Centromere Associations in Mouse Spermatocyte Meiosis
Authors: Chuong Hoa H. , Eyster Craig , Lee Chih-Ying , Pezza Roberto J. , Dawson Dean
Published: February 2018

In meiosis, crossovers between homologous chromosomes link them together. This enables them to attach to microtubules of the meiotic spindle as a unit, such that the homologs will be pulled away from one another at anaphase I. Homologous pairs can sometimes fail to become linked by crossovers. In some organisms, these non-exchange partners are still able segregate properly. In several organisms, associations between the centromeres of non-exchange partners occur in meiotic prophase. These associations have been proposed to promote segregation in meiosis I. But how centromere pairing could promote subsequent proper segregation is unclear. Here we report that meiotic centromere pairing if chromosomes in mouse spermatocytes allows the formation of an association between chromosome pairs. We find that peri-centromeric heterochromatin connections tether the centromeres of chromosome pairs after dissolution of centromere paring. Our results suggest that, in mouse spermatocytes, heterochromatin maintains the association of chromosome centromeres in the absence crossing-over.
A dynamic model of organizational resilience: adaptive and anchored approaches
Authors: Ishak Andrew Waguih , Williams Elizabeth Ann
Published: February 2018

Purpose

Organizations of all types desire to be imbued with resilience, or the ability to withstand and bounce back from difficult events (Richardson, 2002; Walsh 2003). But resilience does not play the same role in every organization. Previous research (Weick and Sutcliffe, 2011) has argued that organizations can be more or less resilient. For high reliability organizations (HROs) such as fire crews and emergency medical units, resilience is a defining feature. Due to the life-or-death nature of their work, the ability to be successful in the face of difficult events is imperative to the process of HROs. The paper aims to discuss these issues.

Design/methodology/approach

This is a theory piece.

Findings

The authors put forth a dual-spectrum model that introduces adaptive and anchored approaches to organizational resilience.

Research limitations/implications

There are organizations for which resilience is only enacted when the organization must overcome difficult events. And at the other end are organizations that may not enact resilience in difficult times, and therefore fail or deteriorate. But while it has been shown that organizations can be more or less resilient, there has been little attention paid to how organizations may have differing types of resilience.

Originality/value

In this piece, the authors theorize that resilience may differ in type between organizations. Drawing on theoretical approaches to resilience from communication (Buzzanell, 2010), organizational behavior (Weick and Sutcliffe, 2011), and motivational psychology (Dweck, 2016), the authors introduce a model that views resilience as a dynamic construct in organizations. The authors argue that an organization’s resilience-centered actions affect – and are determined by – its approach to Buzzanell’s (2010) five communicative processes of resilience. The authors offer testable propositions, as well as theoretical and practical implications from this model, not only for HROs, but for all organizations.
Gokuldhaam Society: a case on transportation planning
Authors: Pandey Peeyush , Sengupta Tuhin
Published: February 2018

Subject area

The subject areas are Operations Management, Operations Research, Transportation and Logistics.

Study level/applicability

The following courses (MBA/Post Graduate level) can use the case as part of their teaching material: Applied Forecasting Techniques; Optimization Methods; Operations Research.

Case overview

The case details a problem faced by the Gokuldhaam Society. The society was located a great distance from the city, as the majority of the residents who live in the society work in the nearby industrial area. To cater to the daily needs of residents, the society has shuttle buses plying to and from the city at different times during the day. However, due to operational inefficiencies, the administration faced excessive transportation costs. Looking for advice in this regard, the chairman of the society contacted the Head of Department at Operations Management, Indira Institute of Management, Indore hoping to find a way to reduce some of the operational costs.

Expected learning outcomes

The expected learning outcomes are as follows: to make the students apply two different stationary time series forecasting techniques to a real-life problem and data set; to make the students carefully choose a specific trend-based time series forecasting technique due to the inherent constraints in the availability of data set; and to make students appreciate the importance of application of linear programming in a time series problem.

Supplementary materials

Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code

CSS 9 Operations and logistics
Development and testing of three unique scales measuring the brand image of nursing
Authors: Godsey Judi Allyn , Hayes Tom , Schertzer Clinton , Kallmeyer Robert
Published: February 2018

Purpose

Nurses have been called to be leaders in the transformation of health care and to help improve health-care access for the nation’s most vulnerable populations. However, to lead health-care transformation, the profession of nurses must first see themselves as leaders. Unfortunately, nursing has been described as lacking cohesiveness and failing to communicate a consistent brand image. No empirically tested quantitative tools exist to measure the brand identity of nursing, making it difficult to assess where the profession stands in regard to the mantel of leadership. The purpose of this study was to develop empirically sound instruments which could measure nurses’ perceptions of their professional brand image. A total of three scales were developed and then tested: The Nursing Brand Image Scale, Nursing’s Current Brand Position Scale and Nursing’s Desired Brand Position Scale.

Design/methodology/approach

The factor structure and internal consistency reliability of each scale were examined following survey administration to a national sample of registered nurses. Principal component analyses were used to explore the factor structure of each scale. Item reduction was achieved through examination of the loading of items across the factors and the impact of the item on internal consistency reliability.

Findings

Respondents to the survey were nursing alumni who received a baccalaureate or master’s degree in nursing at a private, mid-western university, and nursing faculty affiliated with a private, collegiate network (n = 286). For all scales, principal component analysis showed no inter-item correlations >0.9 or <0.1. The Kaiser–Meyer–Olkin measure for sampling adequacy was high and Bartlett’s test of sphericity was significant (p < 0001). The internal consistency reliability of each of the three scales was good to excellent. Current brand position mean scores were highest for the factor “caring advocates for patients/public”, and lowest on “influential leaders”. The most desired brand position mean scores were highest and rated similarly for factors “influential leaders” and “patient-centered caregivers”.

Originality/value

This study provides strong preliminary evidence for the factor structure and internal consistency reliability for each of the three scales and represents an important first step toward quantitatively measuring the brand image of nursing. However, results suggest there is work to be done if nursing is to formulate and adopt a brand image that consistently reinforces their role as leaders. Further testing of the scales with other nursing populations, the general public and with larger sample sizes is recommended.