bluuebunny/crossref_metadata_2025 huggingface dataset:
Screening Laboratory Testing in Asymptomatic Minor Pediatric Blunt Trauma Leads to Unnecessary Needle Sticks
Authors: Badru Faidah , Osei Hector , Munoz-Abraham Armando Salim , Saxena Saurabh , Breeden Robert , Piening Nicholas , Starr David , Xu Perry , Greenspon Jose , Fitzpatrick Colleen M. , Villalona Gustavo A. , Chatoorgoon Kaveer
Published: April 2019

Objective

Screening blood work after minor injuries is common in pediatric trauma. The risk of missed injuries versus diagnostic necessity in an asymptomatic patient remains an ongoing debate. We evaluated the clinical utility of screening blood work in carefully selected asymptomatic children after minor trauma.

Methods

Patients seen at a level 1 pediatric center with “minor trauma” for blunt trauma between 2010 and 2015 were retrospectively reviewed. Exclusion criteria were age <4 of >18 years, a Glasgow Coma Scale score of <15, penetrating trauma, nonaccidental trauma, hemodynamic instability, abdominal findings (pain, distension, bruising, tenderness), hematuria, pelvic/femur fracture, multiple fractures, and operative intervention. Data abstraction included demographics, blood work, interventions, and disposition.

Result

A total of 1308 patients were treated during the study period. Four hundred thirty-three (33%) met inclusion criteria. Mean ± SD age was 12.7 ± 4 years (range, 4–18 years), and 59% were male. Seventy-eight percent were discharged home from the emergency department. All patients had blood work. Twenty-eight percent had at least one abnormal laboratory value. The most common abnormal blood work was leukocytosis (16%). Thirty percent had an intervention, and none prompted by abnormal blood work. One patient had an intra-abdominal finding (psoas hematoma).

Conclusion

When appropriately selected, screening laboratory testing in asymptomatic minor pediatric blunt trauma patients leads to unnecessary needle sticks without significant advantage.
Trends in Pediatric Poisoning-Related Emergency Department Visits: 2001–2011
Authors: Kline Jaclyn N. , Badolato Gia M. , Goyal Monika K.
Published: April 2019

Objectives

We sought to understand the burden of pediatric poisonings on the health care system by characterizing poisoning-related emergency department (ED) visits among children on a national level.

Methods

This was a repeated cross-sectional analysis of the National Hospital Ambulatory Medical Care Survey from 2001 to 2011 of children 21 years or younger who presented to an ED. We measured annual rates of visits, trends over time, and patient and visit characteristics associated with poisoning-related ED visits using multivariable logistic regression. We also compared accidental to intentional poisonings.

Results

There were an estimated 713,345 ED visits per year for poisoning in children, and intentional poisoning–related visits increased over the study period (P trend < 0.001). Compared with all other ED visits, poisoning-related ED visits were more common among males (adjusted odds ratio [aOR], 1.44; 95% confidence interval [CI], 1.26–1.64) and uninsured patients (aOR, 1.26; 95% CI, 1.05–1.51). Poisoned children were more likely to arrive by ambulance (aOR, 3.38; 95% CI, 2.85–4.01) and be admitted (aOR, 1.35; 95% CI, 1.12–1.61). Compared with accidental poisonings, intentional poisonings were more common as age increased (aOR, 1.16; 95% CI, 1.13–1.92) and in children of non-Hispanic black race/ethnicity (aOR, 1.81; 95% CI, 1.12–2.93) and more likely to be associated with ambulance arrival (aOR, 1.49; 95% CI, 1.07–2.08) and hospital admission (aOR, 1.76; 95% CI, 1.25–2.48).

Conclusions

Poisoning-related ED visits among children have remained stable, with significant increase in intentional ingestions from 2001 to 2011. Poisoned children, and particularly those with intentional poisonings, require more health care resources than children with other health concerns. More study is needed on circumstances leading to pediatric poisonings, so that preventive efforts can be targeted appropriately.
Content Validation of Clinical Evidence Related to Self-Care Deficits of Patients With Stroke
Authors: Oliveira-Kumakura Ana Railka de Souza , da Silva Kelly Cristina Rodrigues , Sousa Cássia Milena Freitas Machado , Biscaro Jessica Aparecida , Spagnol Gabriela Salim , Morais Sheila Coelho Ramalho Vasconcelos
Published: April 2019

Objective

The aim of the study was to develop the conceptual and operational definitions for the defining characteristics of each nursing diagnosis related to self-care deficits of patients with stroke and to validate these definitions with experts.

Methods

This was a methodological study. The definitions were evaluated by 32 specialists and analyzed using binomial testing.

Results

All the defining characteristics analyzed were statistically significant (p< .05); three indicators showed agreement at a level lower than the ideal (<0.85).

Conclusion

The definitions achieved validity for measuring self-care deficit for bathing, toileting, dressing, and eating.

Implications for Nursing Practice

These defining characteristics of each nursing diagnosis related to self-care deficits may enable more accurate assessment, driving relevant and individualized action plans in rehabilitation.
Histological Evidence of Intrinsic Muscle Degeneration in Compression Ulnar Neuropathy
Authors: Cha Soo Min , Shin Hyun Dae , Kim Kyeong Hee , Kim Jin Hyun
Published: April 2019

Purpose

We investigated the histological characteristics of the tissues in the intrinsic hand muscles of patients with compressive ulnar neuropathy (CUN) to determine how the compromised nerve influences the target muscle.

Methods

In total, 83 patients underwent surgery for CUN in our institution between March 2015 and August 2017. Of these, 45 patients who met our inclusion/exclusion criteria were initially included in this study. Basic demographic data including age, sex, hand dominance, duration of symptoms, bone mineral density, and clinical stage were evaluated. During the ulnar nerve decompression surgery, a biopsy of the ipsilateral adductor pollicis was performed. Using the biopsy samples, we analyzed the tissue composition and degree of degeneration, and investigated the association with demographic factors and clinical status.

Results

The ratio of muscle/connective tissue/fat was 62.62 ± 8.27%/23.44 ± 4.10%/14.16 ± 6.68% in the affected muscle. The ratio was different than that of samples taken from control groups. In samples containing muscle fibers, although the total fat content remained low, fat was consistently concentrated at the fascicular borders, between fascicles (perifascicular fat, 62.3 ± 18.2% of fascicles), and within fascicles (intrafascicular fat, 35.6 ± 11.8% of fascicles). The proportion of centrally nucleated muscle fibers was also significantly elevated (5.58 ± 4.25%; P < 0.001) compared with that of both controls (1.09 ± 1.26%) and the clinical threshold for abnormal central nuclei (3%). Preoperative scores assessed using Gabel and Amadio criteria were positively correlated with the muscle composition (r = 0.89, P < 0.001). In addition, the clinical status was negatively correlated with the degree of fat accumulation and the proportion of centrally nucleated muscle fibers (r = −0.94, P < 0.001, r = −0.82, P < 0.001).

Conclusions

We demonstrated that target muscle in CUN underwent degeneration, which was potentially exacerbated by inflammation, and that the degree of degeneration was correlated with the patient's clinical status. Histologically, reversible recovery of the hand muscles may be possible if decompression of the ulnar nerve is performed at earlier stages.
Serum Lactate and A Relative Change in Lactate as Predictors of Mortality in Patients With Cardiogenic Shock – Results from the Cardshock Study
Authors: Lindholm Matias Greve , Hongisto Mari , Lassus Johan , Spinar Jindrich , Parissis John , Banaszewski Marek , Silva-Cardoso Jose , Carubelli Valentina , Salvatore diSomma , Sionis Alessandro , Mebazaa Alexandre , Veli-Pekka Harjola , Kober Lars
Published: April 2019

Introduction:

Cardiogenic shock complicating acute myocardial infarction has a very high mortality. Our present study focuses on serial measurement of lactate during admission due to cardiogenic shock and the prognostic effect of lactate and a relative change in lactate in patients after admission and the institution of intensive care treatment.

Methods and Results:

This is a secondary analysis of the CardShock study. Data on lactate at baseline were available on 217 of 219 patients.

In the study population, the median baseline lactate was 2.8 mmol/L (min–max range, 0.5–23.1 mmol/L).

At admission, lactate was predictive of 30-day mortality with an adjusted Hazard ratio (HR) of 1.20 mmol/L (95% confidence interval, CI 1.14–1.27). Within the first 24 h of admission, baseline lactate remained predictive of 30-day mortality. Lactate at 6 h had a HR of 1.14 (95% CI 1.06–1.24) and corresponding values at 12 and 24 h had a HR of 1.10 (1.04–1.17), and of HR 1.19 (95% CI 1.07–1.32), respectively. A 50% reduction in lactate within 6 h resulted in a HR of 0.82 (95% CI 0.72–0.94). Corresponding hazard ratios at 12 and 24 h, were 0.87 (95% CI 0.76–0.98) and 0.74 (95% CI 0.60–0.91), respectively.

Conclusion:

The main findings of the present study are that baseline lactate is a powerful predictor of 30-day mortality, lactate at 6, 12, and 24 h after admission are predictors of 30-day mortality, and a relative change in lactate is a significant predictor of survival within the first 24 h after instituting intensive care treatment adding information beyond the information from baseline values.
Changing the Paradigm of Craniofacial Reconstruction
Authors: Bourne Debra A. , Bliley Jacqueline , James Isaac , Donnenberg Albert D. , Donnenberg Vera S. , Branstetter Barton F. , Haas Gretchen L. , Radomsky Elizabeth , Meyer Ernest Michael , Pfeifer Melanie E. , Brown Spencer A. , Marra Kacey G. , Coleman Sydney , Rubin J. Peter
Published: April 2019

Objective:

This study aimed to prospectively assess outcomes for surgical autologous fat transfer (AFT) applied for traumatic and postsurgical craniofacial deformities. The minimally invasive nature of AFT has potential for reduced risk and superior outcomes compared with current reconstructive options.

Background:

Craniofacial deformities have functional and psychosocial sequelae and can profoundly affect quality of life. Traditional reconstructive options are invasive, invasive, complex, and often lack precision in outcomes. Although AFT is safe, effective, and minimally invasive, only anecdotal evidence exists for reconstruction of craniofacial deformities.

Methods:

In this Institutional Review Board-approved prospective cohort study, 20 subjects underwent AFT (average volume: 23.9 ± 13.2 mL). Volume retention over time was determined using high-resolution computed tomography. Flow cytometry was used to assess cellular subpopulations and viability in the stromal vascular fraction. Quality of life assessments were performed. After the completion of 9-month follow-up, 5 subjects were enrolled for a second treatment.

Results:

No serious adverse events occurred. Volume retention averaged 63 ± 17% at 9 months. Three-month retention strongly predicted 9-month retention (r=0.996,P< 0.0001). There was no correlation between the total volume injected and retention. Patients undergoing a second procedure had similar volume retention as the first (P= 0.05). Age, sex, body mass index, and stromal vascular fraction cellular composition did not impact retention. Surprisingly, former smokers had greater volume retention at 9 months compared with nonsmokers (74.4% vs 56.2%,P= 0.009). Satisfaction with physical appearance (P= 0.002), social relationships (P= 0.02), and social functioning quality of life (P= 0.05) improved from baseline to 9 months.

Conclusions:

For craniofacial defects, AFT is less invasive and safer than traditional reconstructive options. It is effective, predictable, and reaches volume stability at 3 months. Patient-reported outcomes demonstrate a positive life-changing impact.
Mindfulness-based interventions for cancer-related pain and depression: a narrative review of current evidence and future potential
Authors: Baxter Jennie , Welsh Holly , Grayer Justin
Published: April 2019

Purpose of review

People with cancer commonly experience persistent pain and psychological distress. Interventions are needed which address the multifactorial nature of pain and depression, yet few studies have examined the impact of mindfulness-based interventions (MBIs) for cancer-related pain and depression.

Recent findings

MBIs for cancer-related pain and depression can be effectively delivered across a range of modalities and show promise for alleviating mood and some physical health symptoms, although not always pain. There is some evidence for the cost-effectiveness of MBIs.

The field of MBIs would benefit from greater methodological rigour and investigation into a broader range of cancer populations to increase the knowledge base and in turn the evidence base on which interventions can be developed to the benefit to patients with cancer-related pain and depression.
Controlling Cell-Free Gene Expression Behavior by Tuning Membrane Transport Properties
Authors: Caveney Patrick M. , Dabbs Rosemary M. , McClintic William T. , Elizabeth Norred S. , Patrick Collier C. , Simpson Michael L.
Published: April 2019

Controlled transport of molecules across boundaries for energy exchange, sensing, and communication is an essential step toward cell-like synthetic systems. This communication between the gene expression compartment and the external environment requires reaction chambers that are permeable to molecular species that influence expression. In lipid vesicle reaction chambers, species that support expression – from small ions to amino acids – may diffuse across membranes and amplify protein production. However, vesicle-to-vesicle variation in membrane permeability may lead to low total expression and high variability in this expression. We demonstrate a simple optical treatment method that greatly reduces the variability in membrane permeability. When transport across the membrane was essential for expression, this optical treatment increased mean expression level by ~6-fold and reduced expression variability by nearly two orders of magnitude. These results demonstrate membrane engineering may enable essential steps toward cell-like synthetic systems. The experimental platform described here provides a means of understanding controlled transport motifs in individual cells and groups of cells working cooperatively through cell-to-cell molecular signaling.
Urine proteome changes in rats with approximately ten tumor cells subcutaneous inoculation
Authors: Wei Jing , Meng Wenshu , Gao Youhe
Published: April 2019

Biomarkers are changes associated with the disease. Without homeostatic control, urine accumulates very early changes and is an ideal biomarker source. Usually, we performed urinary biomarker studies involving at least thousands of tumor cells. But no tumor starts from a thousand tumor cells. Can we observe any urine proteome changes in rats with approximately ten tumor cells subcutaneous inoculation? Here, we serially diluted Walker-256 carcinosarcoma cells to a concentration of 102/mL and subcutaneously inoculated 0.1 mL of these cells into nine rats. Urine proteomes on days 0, 13 and 21 were profiled by LC-MS/MS analysis and studied with unsupervised clustering analysis. Samples at three time points were almost clustered together, indicating a good consistency in these nine rats. Differential proteins on days 13 and 21 were mainly associated with cell adhesion, autophagic cell death, changes in extracellular matrix organization, angiogenesis, and the pentose phosphate pathway. All of these enriched functional processes were reported to contribute to tumor progression and could not be enriched through random allocation analysis. Our results indicated that 1) the urine proteome reflects changes associated with cancer even with approximately ten tumor cells in the body and that 2) the urine proteome reflects pathophysiological changes in the body with extremely high sensitivity and provides potential for a very early screening process of clinical patients.
Small Glycols Discover Cryptic Pockets on Proteins for Fragment-based Approaches
Authors: Bansia Harsh , Mahanta Pranjal , Yennawar Neela H , Ramakumar Suryanarayanarao
Published: April 2019

Cryptic pockets are visible in ligand-bound protein structures but are occluded in unbound structures. Utilizing these pockets in fragment-based drug-design provides an attractive option for proteins not tractable by classical binding sites. However, owing to their hidden nature, they are difficult to identify. Here, we show that small glycols find cryptic pockets on diverse set of proteins. Initial crystallography experiments serendipitously revealed the ability of ethylene glycol, a small glycol, to identify a cryptic pocket on W6A mutant of RBSX protein (RBSX-W6A). Explicit-solvent molecular dynamics (MD) simulations of RBSX-W6A with exposed-state of the cryptic pocket (ethylene glycol removed) revealed closure of the pocket reiterating that cryptic pockets in general prefer to stay in closed-state in absence of the ligands. Also, no change in the pocket was observed for simulations of RBSX-W6A with occluded-state of the cryptic pocket, suggesting that water molecules are not able to open the cryptic pocket. “Cryptic-pocket finding” potential of small glycols was then supported and generalized through additional crystallography experiments, explicit-cosolvent MD simulations, protein dataset construction and analysis. The cryptic pocket on RBSX-W6A was found again upon repeating the crystallography experiments with another small glycol, propylene glycol. Use of ethylene glycol as probe molecule in cosolvent MD simulations led to the enhanced sampling of the exposed-state of experimentally observed cryptic sites on test set of two proteins (Niemann-Pick C2, Interleukin-2). Further, analyses of protein structures with validated cryptic sites showed that ethylene glycol molecules binds to sites on proteins (G-actin, Myosin II, Bcl-xL, Glutamate receptor 2) which become apparent upon binding of biologically relevant ligands. Our study thus suggests potential application of the small glycols in experimental and computational fragment-based approaches to identify cryptic pockets in apparently undruggable and/or difficult targets, making these proteins amenable to drug-design strategies.
Human Aging DNA Methylation Signatures are Conserved but Accelerated in Cultured Fibroblasts
Authors: Sturm Gabriel , Cardenas Andres , Bind Marie-Abèle , Horvath Steve , Wang Shuang , Wang Yunzhang , Hägg Sara , Hirano Michio , Picard Martin
Published: April 2019

Aging is associated with progressive and site-specific changes in DNA methylation (DNAm). These global changes are captured by DNAm clocks that accurately predict chronological age in humans but relatively little is known about how clocks perform in vitro. Here we culture primary human fibroblasts across the cellular lifespan (∼6 months) and use four different DNAm clocks to show that age-related DNAm signatures are conserved and accelerated in vitro. The Skin & Blood clock shows the best linear correlation with chronological time (r=0.90), including during replicative senescence. Although similar in nature, the rate of epigenetic aging is approximately 62x times faster in cultured cells than in the human body. Consistent with in vivo data, cells aged under hyperglycemic conditions exhibit an approximately three years elevation in baseline DNAm age. Moreover, candidate gene-based analyses further corroborate the conserved but accelerated biological aging process in cultured fibroblasts. Fibroblasts mirror the established DNAm topology of the age-related ELOVL2 gene in human blood and the rapid hypermethylation of its promoter cg16867657, which correlates with a linear decrease in ELOVL2 mRNA levels across the lifespan. Using generalized additive modeling on twelve timepoints across the lifespan, we also show how single CpGs exhibit loci-specific, linear and nonlinear trajectories that reach rates up to −47% (hypomethylation) to +23% (hypermethylation) per month. Together, these high temporal resolution global, gene-specific, and single CpG data highlight the conserved and accelerated nature of epigenetic aging in cultured fibroblasts, which may constitute a system to evaluate age-modifying interventions across the lifespan.

Graphical Abstract
TRIM5α restricts flavivirus replication by targeting the viral protease for proteasomal degradation
Authors: Chiramel Abhilash I. , Meyerson Nicholas R. , McNally Kristin L. , Broeckel Rebecca M. , Montoya Vanessa R. , Méndez-Solís Omayra , Robertson Shelly J. , Sturdevant Gail L. , Lubick Kirk J. , Nair Vinod , Youseff Brian H. , Ireland Robin M. , Bosio Catharine M. , Kim Kyusik , Luban Jeremy , Hirsch Vanessa M. , Taylor R. Travis , Bouamr Fadila , Sawyer Sara L. , Best Sonja M.
Published: April 2019

Tripartite motif-containing protein 5α (TRIM5α) functions as a cellular antiviral restriction factor with exquisite specificity towards the capsid lattices of retroviruses. The relative avidity of TRIM5α binding to retrovirus capsids directly impacts primate species susceptibility to infection, but the antiviral role of TRIM5α is thought limited to retroviruses. In contrast to this current understanding, here we show that both human and rhesus TRIM5α possess potent antiviral function against specific flaviviruses through interaction with the viral protease (NS2B/3) to inhibit virus replication. Importantly, TRIM5α was essential for the antiviral function of IFN-I against sensitive flaviviruses in human cells. However, TRIM5α was ineffective against mosquito-borne flaviviruses (yellow fever, dengue, and Zika viruses) that establish transmission cycles in humans following emergence from non-human primates. Thus, TRIM5α is revealed to possess remarkable plasticity in recognition of diverse virus families, with potential to influence human susceptibility to emerging flaviviruses of global concern.
An Integrative Approach for Fine-Mapping Chromatin Interactions
Authors: Jaroszewicz Artur , Ernst Jason
Published: April 2019

Chromatin interactions play an important role in genome architecture and regulation. The Hi-C assay generates such interactions maps genome-wide, but at relatively low resolutions (e.g., 5-25kb), which is substantially larger than the resolution of transcription factor binding sites or open chromatin sites that are potential sources of such interactions. To predict the sources of Hi-C identified interactions at a high resolution (e.g., 100bp), we developed a computational method that integrates ChIP-seq data of transcription factors and histone marks and DNase-seq data. Our method,χ-SCNN, uses this data to first train a Siamese Convolutional Neural Network (SCNN) to discriminate between called Hi-C interactions and non-interactions.χ-SCNN then predicts the high-resolution source of each Hi-C interaction using a feature attribution method. We show these predictions recover original Hi-C peaks after extending them to be coarser. We also showχ-SCNN predictions enrich for evolutionarily conserved bases, eQTLs, and CTCF motifs, supporting their biological significance.χ-SCNN provides an approach for analyzing important aspects of genome architecture and regulation at a higher resolution than previously possible.

χ-SCNN software is available on GitHub (https://github.com/ernstlab/X-SCNN).
chromoMap: An R package for Interactive Visualization and Annotation of Chromosomes
Authors: Anand Lakshay , Rodriguez Lopez Carlos M.
Published: April 2019

chromoMap is an R package for constructing interactive visualizations of chromosomes/chromosomal regions, and mapping of chromosomal elements (like genes) onto them, of any living organism. The package takes separate tab-delimited files (BED like) to specify the genomic co-ordinates of the chromosomes and the elements to annotate. Each rendered chromosome is composed of continuous loci of specific ranges where each locus, on hover, displays detailed information about the elements annotated within that locus range. By just tweaking parameters of a single function, users can generate a variety of plots that can either be saved as static image or shared as HTML documents. Users can utilize the various prominent features of chromoMap including, but not limited to, visualizing polyploidy, creating chromosome heatmaps, mapping groups of elements, adding hyperlinks to elements, multi-species chromosome visualization.

Availability and implementation

The R package chromoMap is available under the GPL-3 Open Source license. It is included with a vignette for comprehensive understanding of its various features, and is freely available from: https://CRAN.R-project.org/package=chromoMap.

Contact

lakshayanand15@gmail.com

Supplementary information

Supplementary data are available online.
Chemogenomic profiling of anti-leishmanial efficacy and resistance in the related kinetoplastid parasite Trypanosoma brucei
Authors: Collett Clare F , Kitson Carl , Baker Nicola , Steele-Stallard Heather B. , Santrot Marie-Victoire , Hutchinson Sebastian , Horn David , Alsford Sam
Published: April 2019

The arsenal of drugs used to treat leishmaniasis, caused by Leishmania spp., is limited and beset by toxicity and emergent resistance. Furthermore, our understanding of drug mode-of-action and potential routes to resistance is limited. Forward genetic approaches have revolutionised our understanding of drug mode-of-action in the related kinetoplastid parasite, Trypanosoma brucei. Therefore, we screened our genome-scale T. brucei RNAi library in the current anti-leishmanial drugs, sodium stibogluconate (antimonial), paromomycin, miltefosine and amphotericin-B. Identification of T. brucei orthologues of the known Leishmania antimonial and miltefosine plasma membrane transporters effectively validated our approach, while a cohort of 42 novel drug efficacy determinants provides new insights and serves as a resource. Follow-up analyses revealed the antimonial selectivity of the aquaglyceroporin, TbAQP3. A lysosomal major facilitator superfamily transporter contributes to paromomycin/aminoglycoside efficacy. The vesicle-associated membrane protein, TbVAMP7B, and a flippase contribute to amphotericin-B and miltefosine action, and are potential cross-resistance determinants. Finally, multiple phospholipid-transporting flippases, including the T. brucei orthologue of the Leishmania miltefosine transporter, a putative β-subunit/CDC50 co-factor, and additional membrane-associated hits, affect amphotericin-B efficacy, providing new insights into mechanisms of drug uptake and action. The findings from this orthology-based chemogenomic profiling approach substantially advance our understanding of anti-leishmanial drug action and potential resistance mechanisms, and should facilitate the development of improved therapies, as well as surveillance for drug-resistant parasites.

Importance

Leishmaniasis is a devastating disease caused by the Leishmania parasites and is endemic to a wide swathe of the tropics and sub-tropics. While there are drugs available for the treatment of leishmaniasis, these suffer from various challenges, including the spread of drug resistance. Our understanding of anti-leishmanial drug action and the modes of drug resistance in Leishmania is limited. The development of genetic screening tools in the related parasite, Trypanosoma brucei, has revolutionised our understanding of these processes in this parasite. Therefore, we applied these tools to the anti-leishmanial drugs, identifying T. brucei orthologues of known Leishmania proteins that drive drug uptake, as well as a panel of novel proteins not previously associated with anti-leishmanial drug action. Our findings substantially advance our understanding of anti-leishmanial mode-of-action and provide a valuable starting point for further research.
γ-Linolenic acid increases expression of key regulators of lipid metabolism in human skeletal muscle cells
Authors: Baker L.A , Martin N.R.W , Player D.J , Lewis M.P
Published: April 2019

Control of skeletal muscle fat metabolism is regulated acutely through Peroxisome Proliferator Activated Receptor (PPAR) δ activation and its downstream intracellular targets. The purpose of this study was to determine whether fatty acids with high binding affinity for PPARδ can elevate the expression of genes related to fatty acid oxidation and indicators of mitochondrial biogenesis in cultured human skeletal myotubes. Myotubes were treated for 72 hours with one of four conditions: (i) Control (CON); (ii) Eicosapentaenoic acid (EPA 250μM); (iii) γ-linolenic acid (γ-LA 250μM); (iv) PPARδ Agonist (GW501516 10nM). Incubation with γ-LA induced increases in the gene expression of CD36 (p= 0.005), HADHA (p= 0.022) and PDK4 (p=0.025) in comparison with CON, with no further differences observed between conditions. Furthermore, intensity of MitoTracker® Red immunostaining in myotubes increased following incubation with γ-LA (p≤ 0.001) and EPA (p= 0.005) however these trends were not mirrored in the expression of PGC-1α as might be expected. Overall, γ-LA elevates levels the transcription of key intracellular regulators of lipid metabolism and transport in human myotubes, which may be clinically beneficial in the control of metabolic diseases.
Multiple Long-read Sequencing Survey of Herpes Simplex Virus Lytic Transcriptome
Authors: Tombácz Dóra , Balázs Zsolt , Gulyás Gábor , Csabai Zsolt , Boldogkoi Miklós , Snyder Michael , Boldogkoi Zsolt
Published: April 2019

Long-read sequencing (LRS) has become increasingly important in RNA research due to its strength in resolving complex transcriptomic architectures. In this regard, currently two LRS platforms have demonstrated adequate performance: the Single Molecule Real-Time Sequencing by Pacific Biosciences (PacBio) and the nanopore sequencing by Oxford Nanopore Technologies (ONT). Even though these techniques produce lower coverage and are more error prone than short-read sequencing, they continue to be more successful in identifying transcript isoforms including polycistronic and multi-spliced RNA molecules, as well as transcript overlaps. Recent reports have successfully applied LRS for the investigation of the transcriptome of viruses belonging to various families. These studies have substantially increased the number of previously known viral RNA molecules. In this work, we used the Sequel and MinION technique from PacBio and ONT, respectively, to characterize the lytic transcriptome of the herpes simplex virus type 1 (HSV-1). In most samples, we analyzed the poly(A) fraction of the transcriptome, but we also performed random oligonucleotide-based sequencing. Besides cDNA sequencing, we also carried out native RNA sequencing. Our investigations identified more than 160 previously undetected transcripts, including coding and non-coding RNAs, multi-splice transcripts, as well as polycistronic and complex transcripts. Furthermore, we determined previously unsubstantiated transcriptional start sites, polyadenylation sites, and splice sites. A large number of novel transcriptional overlaps were also detected. Random-primed sequencing revealed that each convergent gene pair produces non-polyadenylated read-through RNAs overlapping the partner genes. Furthermore, we identified novel replication-associated transcripts overlapping the HSV-1 replication origins, and novel LAT variants with very long 5’ regions, which are co-terminal with the LAT-0.7kb transcript. Overall, our results demonstrated that the HSV-1 transcripts form an extremely complex pattern of overlaps, and that entire viral genome is transcriptionally active. In most viral genes, if not in all, both DNA strands are expressed.
Nectar- and stigma-specific expression of a chitinase could partially protect against fire blight in certain apples
Authors: Kurilla Anita , Toth Timea , Dorgai Laszlo , Darula Zsuzsanna , Lakatos Tamas , Silhavy Daniel , Kerenyi Zoltan , Dallmann Geza
Published: April 2019

To attract pollinators many angiosperms secrete stigma exudate and nectar in their flowers. As these nutritious fluids are ideal infection points for pathogens, both secretions contain various antimicrobial compounds. Erwinia amylovora, the causing bacterium of the devastating fire blight apple disease, is the model pathogen that multiplies in flower secretions and infects through the nectaries. Although Erwinia resistant apples are not available, certain cultivars are tolerant. It was reported that in stigma infection assay, the ‘Freedom’ cultivar was Erwinia tolerant while the ‘Jonagold’ was susceptible. We hypothesized that differences in the nectar protein compositions lead to different susceptibility. Indeed we found that an acidic chitinase III protein (Machi3-1) selectively accumulates in the nectar and stigma of the ‘Freedom’ cultivar. We demonstrate that MYB binding site containing repeats of the ‘Freedom’ Machi3-1 promoter are responsible for the strong nectar- and stigma-specific expression. As we found that in vitro the Machi3-1 protein impairs growth and biofilm formation of Erwinia at physiological concentration, we propose that the Machi3-1 contribute to the tolerance by inhibiting Erwinia multiplication in the stigma exudate and in the nectar. We show that the Machi3-1 allele was introgressed from Malus floribunda 821 into different apple cultivars including the ‘Freedom’.

Highlight

Certain apple cultivars accumulate to high levels in their nectar and stigma an acidic chitinase III protein that can protect against pathogens including fire blight disease causing Erwinia amylovora
ADHD symptoms map onto noise-driven structure-function decoupling between hub and peripheral brain regions
Authors: Hearne Luke J. , Lin Hsiang-Yuan , Sanz-Leon Paula , Tseng Wen-Yih Isaac , Gau Susan Shur-Fen , Roberts James A. , Cocchi Luca
Published: April 2019

Adults with childhood-onset attention-deficit hyperactivity disorder (ADHD) show altered whole-brain connectivity. However, the relationship between structural and functional brain abnormalities, the implications for the development of life-long debilitating symptoms, and the underlying mechanisms remain uncharted. We recruited a unique sample of 80 medication-naive adults with a clinical diagnosis of childhood-onset ADHD without psychiatric comorbidities, and 123 age-, sex-, and intelligence-matched healthy controls. Structural and functional connectivity matrices were derived from diffusion spectrum imaging and multi-echo resting-state functional MRI data. Hub, feeder, and local connections were defined using diffusion data. Individual-level measures of structural connectivity and structure-function coupling were used to contrast groups and link behavior to brain abnormalities. Computational modeling was used to test possible neural mechanisms underpinning observed group differences in the structure-function coupling. Structural connectivity did not significantly differ between groups but, relative to controls, ADHD showed a reduction in structure-function coupling in feeder connections linking hubs with peripheral regions. This abnormality involved connections linking fronto-parietal control systems with sensory networks. Crucially, lower structure-function coupling was associated with higher ADHD symptoms. Results from our computational model further suggest that the observed structure-function decoupling in ADHD is driven by heterogeneity in neural noise variability across brain regions. By highlighting a neural cause of a clinically meaningful breakdown in the structure-function relationship, our work provides novel information on the nature of chronic ADHD. The current results encourage future work assessing the genetic and neurobiological underpinnings of neural noise in ADHD, particularly in brain regions encompassed by fronto-parietal systems.
Bean yellow mosaic virus infecting broad bean in the green belt of Córdoba, Argentina
Authors: Rodríguez Pardina Patricia , Nome Claudia , Reyna Pablo , Muñoz Nacira , Argüello Caro Evangelina , Luque Andrés , Debat Humberto Julio
Published: April 2019

Broad bean (Vicia faba L) is the fourth most important pulse crop in the world. In Argentina, broad bean production was of 1,841 hectares and 16,500 tons during the 2017 growing season. Broad bean is commonly used in rotations; especially by farmers located in “green belts” that are peri-urban areas surrounding large cities that include horticultural family farms. Plants showing marked foliar mosaic symptoms, typical of viral infection, were collected during the 2015 growing season in the green belt of Córdoba city, Argentina. Preparations of symptomatic tissues were mechanically inoculated onto healthy broad bean plants in the greenhouse, which developed symptoms similar to those observed in the field. In addition, symptomatic samples were positive when tested by indirect ELISA with the anti-potyvirus group monoclonal antibody. Further, flexuous filamentous particles typical of potyviruses were observed under the electronic microscope on dip preparations. Lastly, total RNA was extracted from a symptomatic leaf and high-throughput sequenced, which allowed the assembly of a single virus sequence corresponding to a new highly divergent strain of Bean yellow mosaic virus (BYMV). Phylogenetic insights clustered this Argentinean broad bean isolate (BYMV-ARGbb) within group IX of BYMV. Given the economical importance of this virus and its associated disease, the results presented here are a pivotal first step oriented to explore the eventual incidence and epidemiological parameters of BYMV in broad bean in Argentina.
A conserved protein, BcmA, mediates motility, biofilm formation, and host colonisation in Adherent InvasiveEscherichia coli
Authors: Cogger-Ward Robert , Collins Adam , McLean Denise , Dehinsilu Jacob , Huett Alan
Published: April 2019

Adherent InvasiveEscherichia coli(AIEC) is a non-diarrhoeagenic intestinalE. colipathotype associated with Crohn’s Disease. AIEC pathogenesis is characterised by biofilm formation, adhesion to and invasion of intestinal epithelial cells, and intracellular replication within epithelial cells and macrophages. Here, we identify and characterise a protein in the prototypical AIEC strain LF82 which is required for efficient biofilm formation and dispersal – LF82_p314. LF82 ΔLF82_314have defective swimming and swarming motility, indicating LF82_p314 is important for flagellar-mediated motility, and thus surface colonisation and biofilm dispersal. Flagellar morphology and chemotaxis in liquid appear unaffected by deletion ofLF82_314, suggesting LF82_p314 does not elicit an effect on flagella biogenesis or environmental sensing. Flagellar motility has been implicated in AIEC virulence, therefore we assessed the role of LF82_p314 in host colonisation using aCaenorhabditis elegansmodel. We found that LF82 ΔLF82_314have an impaired ability to colonise theC. eleganscompared to wild-type LF82. Phylogenetic analysis showed thatLF82_314is conserved in several major enterobacterial pathogens, and suggests the gene may have been acquired horizontally in several genera. Our data suggests LF82_p314 may be a novel component in the flagellar motility pathway and is a novel determinant of AIEC colonisation. Our findings have potential implications not only for the pathogenesis of Crohn’s Disease, but also for the course of infection in several major bacterial pathogens. We propose a new designation forLF82_314,biofilmcoupled tomotilityA, orbcmA.

Author summary

Adherent InvasiveEscherichia coli(AIEC) are a group of bacteria implicated in the pathogenesis of Crohn’s Disease, a chronic inflammatory bowel disease with no cure. Critical to the process of many bacterial infections is the ability of bacteria to swim towards and colonise the host surface using specialised, propeller-like appendages called flagella. In this paper, we describe a novel protein – LF82_p314 (BcmA) – which is required for efficient flagella-mediated motility and surface colonisation in AIEC. Using a nematode worm (Caenorhabditis elegans) infection model, we show that LF82_p314 enables effective colonisation of theC. elegansgut, suggesting a role for the protein during human infection. These findings indicate BcmA is significant for initial colonisation of the human gut by AIEC, and therefore the onset of Crohn’s Disease.
Dynamical effects on superradiant THz emission from an undulator
Authors: Geloni Gianluca , Tanikawa Takanori , Tomin Sergey
Published: April 2019

Superradiant emission occurs when ultra-relativistic electron bunches are compressed to a duration shorter than the wavelength of the light emitted by them. In this case the different electron contributions to the emitted field sum up in phase and the output intensity scales as the square of the number of electrons in the bunch. In this work the particular case of superradiant emission from an undulator in the THz frequency range is considered. An electron bunch at the entrance of a THz undulator setup has typically an energy chirp because of the necessity to compress it in magnetic chicanes. Then, the chirped electron bunch evolves passing through a highly dispersive THz undulator with a large magnetic field amplitude, and the shape of its longitudinal phase space changes. Here the impact of this evolution on the emission of superradiant THz radiation is studied, both by means of an analytical model and by simulations.
Differences in state- and district-level stakeholders’ perceptions of curriculum coherence and school impact in national curriculum reform
Authors: Sullanmaa Jenni , Pyhältö Kirsi , Pietarinen Janne , Soini Tiina
Published: April 2019

Purpose

Shared understandings of curriculum reform within and between the levels of the educational system are suggested to be crucial for the reform to take root. The purpose of this paper is to explore variation in perceived curriculum coherence and school impact among state- and district-level stakeholders.

Design/methodology/approach

The participants (n=666) included state- and district-level stakeholders involved in a national curriculum reform in Finland. Latent profile analysis was employed to identify profiles based on participants’ perceptions of the core curriculum’s coherence and the reform’s impact on school development.

Findings

Two profiles were identified: high coherence and impact, and lower consistency of the intended direction and impact. State-level stakeholders had higher odds of belonging to the high coherence and impact profile than their district-level counterparts.

Practical implications

The results imply that more attention needs to be paid in developing a shared and coherent understanding particularly of the intended direction of the core curriculum as well as the reform’s effects on school-level development among state- and district-level stakeholders.

Originality/value

The study contributes to the literature on curriculum reform by shedding light on the variation in perceived curriculum coherence and school impact of those responsible for a large-scale national curriculum reform process at different levels of the educational system.
“Walking the talk” in times of recession: the case of corporate social responsibility in Greece
Authors: Papacharalampous Nikolaos , Papadimitriou Dimitra , Anagnostopoulos Christos
Published: April 2019

Purpose

This study aims to examine the actions of corporate social responsibility (CSR) at a national business context that is firmly defined by prolonged financial crisis. It does so by using a critical view on CSR disclosures in an attempt to get to the heart of the real matter of CSR, from both a thematic content and strategic orientation perspective.

Design/methodology/approach

This study is based on a sample of 50 firms that operate in the Greek market and belong to the most significant sectors of the national economy. Their CSR disclosures are content-analyzed, providing a body of 836 pragmatic CSR actions.

Findings

The key findings of the study denote differences among the examined sectors, with banks and financial services being the most active in terms of CSR actions. Regarding the thematic content, firms choose mainly to implement actions with a societal character, while in terms of strategic orientation, they opt for CSR actions that serve existing cause-related programs without any brand presence. Moreover, profound interest appears for the external business environment, whereas the number of CSR actions with employees’ participation is limited.

Practical implications

The study offers a descriptive account of the actual CSR engagement in Greece amid a prolonged downturn, thus shedding light on the current CSR trends and deficits and helping decision makers embed CSR as an integral part of their business operation.

Originality/value

During adverse economic conditions, this study captures potential discrepancies between the “walk” (doing) and the “talk” (self-reporting) of CSR. In so doing, it contributes to CSR literature by exploring both the “what” and the “how” these actions are implemented.
Progression to intermediate level courses; is a “pass” enough?
Authors: Beatson Nicola J. , Berg David A.G. , Smith Jeffrey K. , Smith-Han Christine
Published: April 2019

Purpose

The purpose of this paper is to test the impact of a rule that affects tertiary students progressing from an introductory level finance course to intermediate level. The rule restricted students from progressing until they achieved a higher grade than just a “pass” mark.

Design/methodology/approach

Archival data were gathered from 11 semesters regarding student performance pre and post the rule being introduced.

Findings

Results show that the rule was associated with an increase in the chances of success at intermediate level for those students enrolled after the rule was introduced.

Practical implications

This paper’s main contribution regards the evidence that increasing prior learning at an introductory level has a positive follow-on effect for students learning at intermediate level. This has a practical implication for educators, as the rule has shown to increase the chance of success for knowledge development in the first year of studies.

Originality/value

The setting for this paper is unique and could potentially be replicated elsewhere. In 1980, Schaffer and Calkins called for an evaluation of the pre-requisites necessary for finance education at the tertiary level, and this paper answer this call stating that pre-requisites can contribute to the academic success of finance students.