bluuebunny/crossref_metadata_2025 huggingface dataset:
Selenoprotein P in Myocardial Infarction With Cardiogenic Shock
Authors: Büttner Petra , Obradovic Danilo , Wunderlich Sebastian , Feistritzer Hans-Josef , Holzwirth Erik , Lauten Philipp , Fuernau Georg , de Waha-Thiele Suzanne , Desch Steffen , Thiele Holger
Published: March 2019

Background:

Reperfusion strategies in acute myocardial infarction (AMI) may result in ischemia reperfusion injury characterized by increased oxidative stress, inflammation, and ultimately death of myocardial tissue which may be of particular importance in infarct-related cardiogenic shock (CS). Many anti-oxidative and immune regulatory processes depend on selenium which in large proportions is bound to circulating selenoprotein P (SelP). Individual SelP patterns may therefore be associated with inflammatory response and possibly mortality in patients with CS post AMI.

Methods:

In the randomized Intra-Aortic Balloon Pump in cardiogenic Shock II (IABP-SHOCK II)-trial, 600 patients with CS complicating AMI were assigned to therapy with or without IABP. In a predefined biomarker substudy of 147 patients, we analyzed SelP levels 1 and 3 days following randomization. Samples were compared with healthy controls and associations with the unspecific inflammatory marker C-reactive protein (CRP) were analyzed.

Results:

Compared with controls SelP levels in patients with infarct-related CS were markedly higher (2.7-fold at day 1 and 5.7-fold at day 3 following AMI, all P < 0.001). Thirty-day mortality was significantly higher in patients with SelP levels above the 75th percentile at day 3 following AMI (26% vs. 46%, P = 0.045). SelP was significantly proportionally correlated with CRP 1 (R2 = 0.762, P < 0.0001) and 3 days (R2 = 0.777 P < 0.0001) following AMI.

Conclusion:

SelP levels are significantly increased post AMI with CS. Higher SelP levels are associated with increased CRP levels indicative for inflammatory processes. Future studies should focus on the characterization of SelP profiles following AMI and the identification of pathomechanisms affected by SelP.
A Randomized Controlled Trial Comparing Learners' Decision-making, Anxiety, and Task Load During a Simulated Airway Crisis Using Two Difficult Airway Aids
Authors: Ambardekar Aditee P. , Rosero Eric B. , Bhoja Ravi , Green Jerry , Rebal Brett A. , Minhajuddin Abu T. , Kosemund Matthew S. , Guttman Oren T. , Mercier David W.
Published: March 2019

Introduction

The American Society of Anesthesiologists (ASA) difficult airway algorithm and the Vortex approach are difficult airway aids. Our objective was to demonstrate that a simpler cognitive model would facilitate improved decision-making during a process such as difficult airway management. We hypothesized the simpler Vortex approach would be associated with less anxiety and task load.

Methods

Medical students were randomized to the ASA algorithm (n = 33) or Vortex approach (n = 34). All learned basic airway techniques on day 1 of their rotation. Next, they watched a video of their respective aid then managed a simulated airway crisis. We assessed decision-making using a seven-point airway management score and a completeness score. Completeness was at least one attempt at each of four techniques (mask ventilation, supraglottic airway, intubation, and cricothyrotomy). Two validated tools, the State-Trait Anxiety Inventory Form Y and the National Aeronautics and Space Administration Task Load Index, were used to assess anxiety and task load.

Results

Students in the Vortex group had higher airway management scores [4.0 (interquartile range = 4.0 to 5.0) vs. 4.0 (3.0 to 4.0), P = 0.0003] and completeness (94.1% vs. 63.6%, P = 0.003). In the ASA group, the means (SD) of National Aeronautics and Space Administration Task Load Index scores of 55 or higher were observed in mental [61.4 (14.4)], temporal [62.3 (22.9)], and effort [57.1 (15.6)] domains. In the Vortex group, only the temporal load domain was 55 or higher [mean (SD) = 57.8 (25.4)]. There was no difference in anxiety.

Conclusions

Medical students perform better in a simulated airway crisis after training in the simpler Vortex approach to guide decision-making. Students in the ASA group had task load scores indicative of high cognitive load.
Tranexamic acid administration following head trauma in a combat setting: Does tranexamic acid result in improved neurologic outcomes?
Authors: Morte Douglas , Lammers Daniel , Bingham Jason , Kuckelman John , Eckert Matthew , Martin Matthew
Published: March 2019

BACKGROUND

Tranexamic acid (TXA) has been shown to decrease mortality and blood product requirements in severely injured patients. Tranexamic acid has also been hypothesized to prevent secondary brain injury in patients with traumatic brain injury. While prior studies have demonstrated improved neurologic outcomes associated with TXA administration in severely injured pediatric patients, no such studies have been performed in adults.

METHODS

A retrospective review of all adult trauma admissions to North Atlantic Treaty Organization hospitals in Iraq and Afghanistan between 2008 and 2015. Univariate and multivariate analysis was used to identify factors associated with TXA administration. Patients without a documented head Abbreviated Injury Scale (AIS) were excluded. Patients were propensity matched based on demographics, mechanism of injury, Injury Severity Score (AIS/ISS), presenting Glasgow Coma Scale (GCS) score, initial vitals/laboratory values, and initial transfusion requirement. Primary outcomes were in-hospital mortality and neurologic outcomes measured by discharge GCS scores. Secondary outcomes were respiratory failure and rates of thromboembolic events.

RESULTS

Four thousand four hundred seventy-six injured patients 18 years or older were evaluated. Two hundred sixty-five (5.9%) of these patients required a massive transfusion in the first 24 hours, and 174 (3.9%) received TXA. The TXA patients had significantly higher ISS, more penetrating injuries, lower presenting GCS, higher incidence of severe head injury (AIS > 3), and higher transfusion requirements. Ninety-two patients were included in the propensity matched cohort. Of these, patients who received TXA had significantly lower mortality rate (0% vs. 10.1%, p = 0.02) and improvement of GCS score to 14 to 15, irrespective of admission GCS compared with patients who did not receive TXA (100% vs. 87%, p = 0.01). There were no significant differences in number of thromboembolic events recorded between the two groups.

CONCLUSION

The TXA administration in adult combat trauma patients was independently associated with decreased mortality and improved neurologic outcomes, with no increase in thromboembolic events. Further study of the possible mechanisms and effect of TXA on brain injury and neurologic outcomes is warranted.

LEVEL OF EVIDENCE

Therapeutic, level IV.
Management of acute appendicitis in adults: A practice management guideline from the Eastern Association for the Surgery of Trauma
Authors: Rushing Amy , Bugaev Nikolay , Jones Christian , Como John J. , Fox Nicole , Cripps Michael , Robinson Bryce , Velopulos Catherine , Haut Elliott R. , Narayan Mayur
Published: March 2019

BACKGROUND

Acute appendicitis (AA) has been considered one of the most common acute surgical conditions in the world. Recent studies, however, have suggested that nonoperative management (NOM) with a course of antibiotics (ABX) may be as effective as surgery in treating appendicitis. As there are evolving perspectives regarding the optimal therapy for appendicitis, we sought to provide recommendations regarding the role of NOM with the administration of antibiotics (antibiotics-first approach) in uncomplicated AA as well as the need for routine interval appendectomy (RIA) in those presenting with appendiceal abscess or phlegmon (AAP) initially managed without appendectomy.

METHODS

A writing group from the Guidelines Committee of the Eastern Association for the Surgery of Trauma (EAST) performed a systematic review and meta-analysis of the current literature regarding appendicitis in adult populations. The Grading of Recommendations Assessment, Development and Evaluation methodology was applied and meta-analyses and evidence profiles generated.

RESULTS

When comparing antibiotics-first therapy to surgery for uncomplicated AA in adult populations, we found that perforation and recurrence of disease were the only outcomes consistently represented in the literature. For perforation, we were unable to make a definitive conclusion based on the degree of heterogeneity among the six randomized controlled trials reviewed. The risk of recurrence at 1 year with antibiotics-first treatment was 15.8% (95% confidence interval, 12.05–118.63). Critical outcomes could not be evaluated with the current literature. In NOM patients for AAP, the risk of recurrence was 24.3% if RIA was not performed (95% confidence interval, 2.74–73.11).

CONCLUSION

Based on the completed meta-analysis and Grading of Recommendations Assessment, Development and Evaluation profiles, we were unable to make a recommendation for or against the antibiotics-first approach as primary treatment for uncomplicated AA. For NOM with AAP, we conditionally recommend against RIA in an otherwise asymptomatic patient. This review reveals multiple limitations of the published literature, leaving ample opportunities for additional research on this topic.

LEVEL OF EVIDENCE

Systematic review, level II.
Electroconvulsive Therapy Practice in the Kingdom of Denmark
Authors: Bjørnshauge Didde , Hjerrild Simon , Videbech Poul
Published: March 2019

Objectives

The aim of this study was to survey and describe the contemporary practice of electroconvulsive therapy (ECT) in the Kingdom of Denmark (Denmark, Greenland, and the Faroe Islands).

Methods

Data regarding number of ECTs and number of patients with different diagnoses treated with ECT were retrieved from the Danish National Patient Registry. In addition, a 45-item questionnaire was sent to all psychiatric departments practicing ECT in Denmark (n = 26), Greenland (n = 1), and the Faroe Islands (n = 1).

Results

According to the Danish National Patient Registry, a total of 21,730 ECTs were administered to 1891 unique patients in 2017. All departments responded to the survey. The psychiatric departments' attitude toward ECT was generally favorable and in accord with official guidelines. Maintenance ECT was used in all departments but one. Bilateral electrode placement was preferred. All departments used a preselected age-based dosing strategy. Involuntary ECT was performed in 96% of the psychiatric departments, but infrequently (3% of all treatments). All departments used a Thymatron (brief pulse) device, and in 71% of the departments, ECT was given in a specialized ECT unit and preanesthetic evaluation was carried out in all departments. The departments reported several different practices regarding documentation and monitoring of treatment effect, patient consent, screening for side effects (including cognitive side effects), and guidelines for the discharge of ECT patients.

Conclusions

Electroconvulsive therapy is frequently used in Denmark, Greenland, and the Faroe Islands in a relatively uniform way in adherence with clinical guidelines.
Electroconvulsive Treatment Utilization for the Inpatient Management of Severe Manic Episodes of Bipolar Disorder
Authors: Patel Rikinkumar S. , Jain Shailesh Bobby , Youssef Nagy A.
Published: March 2019

Objective

Main objectives of the study are to (1) describe the utilization of electroconvulsive treatment (ECT) for the treatment of manic episodes (ME) and (2) examine the effect of early inpatient use of ECT (within 7 days of admission) compared with delayed use on length of stay and cost of inpatient care.

Method

The total sample of 14,005 inpatients with a principal diagnosis of bipolar disorder, ME (2012–2014), from the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project were analyzed using univariate and logistic regressions. This represented data from 4411 hospitals from 45 states in the United States.

Results

The rate of ECT use was higher in young adults (<50 years), female patients, and whites from high-income families. Electroconvulsive treatment was preferred more in private, nonprofit, urban, and teaching hospitals. The percentages of overall hospitals where ECT was administered for mania by region were as follows: 22% in the Northeast, 23% in Midwest. 17% in the South, and 10% in the West. Approximately half (55.3%) of patients received initial ECT session within the first 7 days (median) after admission. Early ECT was associated with significantly shorter (−14.7 days) and less costly (−$41,976) inpatient care per patient.

Conclusions

Patients treated with ECT are generally sicker and more treatment resistant. However, ECT should not be considered only as a “last resort” in the treatment algorithm. Inpatient ECT for patients with MEs if initiated during the first 7 days of hospitalization reduces length of stay and cost.
Analysis of biogenic amines and inorganic elements in Cheonggukjang
Authors: Seo Min-Jeong , Lee Chang-Do , Lee Ji-Na , Yang Hee-Jong , Jeong Do-Youn , Lee Gae-Ho
Published: March 2019

The quantitative analyses of biogenic amines (BAs) in fermented food is one of the critical issues in food safety. Thirty-seven samples were analyzed in order to determine the BA content in Cheonggukjang. Additionally inorganic elements in 6 samples were analyzed using inductively coupled plasma atomic emission spectroscopy and inductively coupled plasma mass spectrometry. The BA content was analyzed using high-performance liquid-chromatography (HPLC) after derivatization of the samples by densyl chloride. Biogenic amines, namely, tryptamine (TRP), 2-phenylethylamine (PHE), putrescine (PUT), cadaverine (CAD), histamine (HIS), tyramine (TYR) spermidine (SPD), and spermine (SPM) were detected by monitoring the absorbance from the samples at 254 nm using the UV-vis detector attached to the HPLC system. The chromatograms were also verified for linearity and accuracy. The results showed that all the correlation coefficients (R2) were over 0.99, while the recovery was 89.7% -103.4%. The average BA contents in Cheonggukjang were as follows: TRP 43.8 mg/kg, PHE 11.8 mg/kg, PUT 10.6 mg/kg, CAD 10.3 mg/kg, HIS 3.8 mg/kg, TYR 113.7 mg/kg, SPD 37.6 mg/kg, SPM 11.5 mg/kg. The average contents of inorganic elements in Cheonggukjang were as follows Na 0.93%, K 0.55%, Ca 0.14%, P 0.30%, Mg 0.11%, S 0.17%, Fe 29.6 mg/kg, Mn 13.4 mg/kg, Zn 17.6 mg/kg, Cu 3.44 mg/kg, Sr 3.21 mg/kg, Mo 1.40 mg/kg, Ba 2.12 mg/kg, Se 0.071 mg/kg, Cd 0.014 mg/kg, As 0.011 mg/kg.
Optimization of fermentation conditions Protaetia brevitarsis seulensis larvae using Bacillus subtilis
Authors: Sim So-Yeon , Jang Sung-Ho , Ahn Hee-Young , Cho Hyun-Dong , Seo Kwon-Il , Cho Young-Su
Published: March 2019

This study aimed to investigate the biological activities of aqueous extract of the edible insect Protaetia brevitarsis seulensis (PB) larvae fermented by Bacillus subtilis KACC 91157. On the other hand, the soluble solids of PB increased reaching the maximum level about 5.6 °Brix after 7 days of fermentation. Protein concentration also increased during the fermentation period and the highest protein content was measured in the PB fermented for 6 days with B. subtilis. Protein content was analyzed by SDS (sodium dodecyl sulfate)-polyacrylamide gel electrophoresis, and it was observed that most of the protein bands were completely degraded after 3 days of fermentation. The phenolic and flavonoid compounds were higher in the fermented group than the non-fermented group. They showed the highest amounts during 2-3 days of fermentation. The highest reducing power and DPPH (α,α’-diphenyl-β-picrylhydrazyl) radical scavenging activity were observed in PB fermented for 3 days, and no major changes occurred during the subsequent fermentation. Similarly, fibrinolytic activity was the highest at the 3rd day of fermentation. This experiment showed that fermentation of PB for 3 days by B. subtilis is the optimum time to achieve the desired physicochemical properties and highest biological activities.
Storage stability of sourdough bread with lactic acid bacteria culture solution and cinnamon extract
Authors: Huh Chang Ki , Shim Ki Hoon
Published: March 2019

This study investigated the changes in moisture content, pH, titrated acidity, Hunter’s color value, textural properties, and retarding retrogradation during the storage of sourdough bread made with lactic acid bacteria culture (LCBC) and cinnamon extract. The measurement results showed that the moisture content and pH of all the samples tended to decrease during the storage period; the CE0 sample exhibited the least variation in moisture content, whereas the CE100 sample showed the least variation in pH. The titrated acidity of all the samples increased during storage, but the extent decreased with the amount of cinnamon extract added. During the storage period, the redness, hardness, and gumminess increased; the whiteness, adhesiveness, springiness, and cohesiveness decreased; and the chewiness decreased after an initial increase. The retarding retrogradation was stronger for the group with LCBC and cinnamon extract, compared to that of the control, whereas the CE50 sample presented the strongest retarding retrogradation effect with the lowest Avrami exponent. These results suggested that the addition of LCBC and cinnamon extract during the manufacture of sourdough bread improved the storage period efficiency and retarding retrogradation.
Integrative analysis of epigenetics data identifies gene-specific regulatory elements
Authors: Schmidt Florian , Marx Alexander , Hebel Marie , Wegner Martin , Baumgarten Nina , Kaulich Manuel , Göke Jonathan , Vreeken Jilles , Schulz Marcel H.
Published: March 2019

Understanding the complexity of transcriptional regulation is a major goal of computational biology. Because experimental linkage of regulatory sites to genes is challenging, computational methods considering epigenomics data have been proposed to create tissue-specific regulatory maps. However, we showed that these approaches are not well suited to account for the variations of the regulatory landscape between cell-types. To overcome these drawbacks, we developed a new method called STITCHIT, that identifies and links putative regulatory sites to genes. Within STITCHIT, we consider the chromatin accessibility signal of all samples jointly to identify regions exhibiting a signal variation related to the expression of a distinct gene. STITCHIToutperforms previous approaches in various validation experiments and was used with a genome-wide CRISPR-Cas9 screen to prioritize novel doxorubicin-resistance genes and their associated non-coding regulatory regions. We believe that our work paves the way for a more refined understanding of transcriptional regulation at the gene-level.
Genome-wide analysis of MIKC-type MADS-box genes in wheat: pervasive duplications may have facilitated adaptation to different environmental conditions
Authors: Schilling Susanne , Kennedy Alice , Pan Sirui , Jermiin Lars S. , Melzer Rainer
Published: March 2019

Background

Wheat (Triticum aestivum) is one of the most important crops worldwide. Given a growing global population coupled with increasingly challenging climate and cultivation conditions, facilitating wheat breeding by fine-tuning important traits such as stress resistance, yield and plant architecture is of great importance. Since they are involved in virtually all aspects of plant development and stress responses, prime candidates for improving these traits are MIKC-type (type II) MADS-box genes.

Results

We present a detailed overview of number, phylogeny, and expression of 201 wheat MIKC-type MADS-box genes, which can be assigned to 15 subfamilies. Homoeolog retention is significantly above the average genome-wide retention rate for wheat genes, indicating that many MIKC-type homoeologs are functionally important and not redundant. Gene expression is generally in agreement with the expected subfamily-specific expression pattern, indicating broad conservation of function of MIKC-type genes during wheat evolution.

We find the extensive expansion of some MIKC-type subfamilies to be correlated with their chromosomal location and propose a link between MADS-box gene duplications and the adaptability of wheat. A number of MIKC-type genes encode for truncated proteins that lack either the DNA-binding or protein-protein interaction domain and occasionally show novel expression patterns, possibly pointing towards neofunctionalization.

Conclusions

Conserved and neofunctionalized MIKC-type genes may have played an important role in the adaptation of wheat to a diversity of conditions, hence contributing to its importance as a global staple food. Therefore, we propose that MIKC-type MADS-box genes are especially well suited for targeted breeding approaches and phenotypic fine tuning.
Distinct immune evasion in APOBEC-enriched, HPV-negative HNSCC
Authors: Messerschmidt Clemens , Obermayer Benedikt , Klinghammer Konrad , Ochsenreither Sebastian , Treue Denise , Stenzinger Albrecht , Glimm Hanno , Fröhling Stefan , Kindler Thomas , Brandts Christian H. , Schulze-Osthoff Klaus , Weichert Wilko , Tinhofer Ingeborg , Klauschen Frederick , Keilholz Ulrich , Beule Dieter , Rieke Damian T.
Published: March 2019

Immune checkpoint inhibition leads to response in some patients with head and neck squamous cell carcinoma (HNSCC). Robust biomarkers are lacking to date.

We analyzed viral status, gene expression signatures, mutational load and mutational signatures in whole exome and RNA-sequencing data of the HNSCC TCGA dataset (N = 496) and a validation set (DKTK MASTER cohort, N = 10). Public single-cell gene expression data from 17 HPV-negative HNSCC were separately re-analyzed.

Among HPV-negative HNSCC, APOBEC3-associated TCW motif mutations but not total single nucleotide variant burden were significantly associated with inflammation. APOBEC3-enriched HPV-negative HNSCC showed higher T-cell inflammation and immune checkpoint expression. Mutations in immune-evasion pathways were enriched in these tumors. APOBEC3B and 3C expression was identified in tumor cells and correlated with tumor inflammation.

We identified an APOBEC-enriched subgroup of HPV-negative HNSCC with a distinct immunogenic phenotype, potentially mediating response to immunotherapy.
The TCR/peptide/MHC complex with a superagonist peptide shows similar interface and reduced flexibility compared to the complex with a self-peptide
Authors: Salutari Ilaria , Martin Roland , Caflisch Amedeo
Published: March 2019

T-cell receptor (TCR) recognition of myelin basic protein (MBP) peptide presented by major histocompatibility complex (MHC) protein HLA-DR2a, one of the MHC class II alleles associated with multiple sclerosis, is highly variable. Interactions in the trimolecular complex between the TCR of MBP83-99-specific T cell clone 3A6 with the MBP-peptide/HLA-DR2a (abbreviated TCR/pMHC) lead to substantially different proliferative responses when comparing the wild-type decapeptide MBP90-99 and a superagonist peptide which differs mainly in the residues that point towards the TCR. Here we investigate the influence of the peptide sequence on the interface and intrinsic plasticity of the TCR/pMHC trimolecular and pMHC bimolecular complexes by molecular dynamics simulations. The intermolecular contacts at the TCR/pMHC interface are similar for the complexes with the superagonist and the MBP self-peptide. The orientation angle between TCR and pMHC fluctuates less in the complex with the superagonist peptide. Thus, the higher structural stability of the TCR/pMHC tripartite complex with the superagonist peptide, rather than a major difference in binding mode with respect to the self-peptide, seems to be responsible for the stronger proliferative response.
Metabolic labeling of RNAs uncovers hidden features and dynamics of the Arabidopsis thaliana transcriptome
Authors: Szabo Emese Xochitl , Reichert Philipp , Lehniger Marie-Kristin , Ohmer Marilena , de Francisco Amorim Marcella , Gowik Udo , Schmitz-Linneweber Christian , Laubinger Sascha
Published: March 2019

Transcriptome analysis by RNA sequencing (RNA-seq) has become an indispensable core research tool in modern plant biology. Virtually all RNA-seq studies provide a snapshot of the steady-state transcriptome, which contains valuable information about RNA populations at a given time, but lacks information about the dynamics of RNA synthesis and degradation. Only a few specialized sequencing techniques, such as global run-on sequencing (GRO-seq), have been applied in plants and provide information about RNA synthesis rates. Here, we demonstrate that RNA labeling with a modified, non-toxic uridine analog, 5-ethynyl uridine (5-EU), in Arabidopsis thaliana seedlings provides insight into the dynamic nature of a plant transcriptome. Pulse-labeling with 5-EU allowed the detection and analysis of nascent and unstable RNAs, of RNA processing intermediates generated by splicing, and of chloroplast RNAs. We also conducted pulse-chase experiments with 5-EU, which allowed us to determine RNA stabilities without the need for chemical inhibition of transcription using compounds such as actinomycin and cordycepin. Genome-wide analysis of RNA stabilities by 5-EU pulse-chase experiments revealed that this inhibitor-free RNA stability measurement results in RNA half-lives much shorter than those reported after chemical inhibition of transcription. In summary, our results show that the Arabidopsis nascent transcriptome contains unstable RNAs and RNA processing intermediates, and suggest that half-lives of plant RNAs are largely overestimated. Our results lay the ground for an easy and affordable nascent transcriptome analysis and inhibitor-free analysis of RNA stabilities in plants.
Proteinarium: Multi-Sample Protein-Protein Interaction Analysis and Visualization Tool
Authors: Armanious David , Schuster Jessica , Tollefson George F. , Agudelo Anthony , DeWan Andrew T. , Istrail Sorin , Padbury James , Uzun Alper
Published: March 2019

Background

Data analysis has become crucial in the post genomic era where the accumulation of genomic information is mounting exponentially. Analyzing protein-protein interactions in the context of the interactome is a powerful approach to understanding disease phenotypes.

Results

We describe Proteinarium, a multi-sample protein-protein interaction network analysis and visualization tool. Proteinarium can be used to analyze data for samples with dichotomous phenotypes, multiple samples from a single phenotype or a single sample. Then, by similarity clustering, the network-based relations of samples are identified and clusters of related samples are presented as a dendrogram. Each branch of the dendrogram is built based on network similarities of the samples. The protein-protein interaction networks can be analyzed and visualized on any branch of the dendrogram. Proteinarium’s input can be derived from transcriptome analysis, whole exome sequencing data or any high-throughput screening approach. Its strength lies in use of gene lists for each sample as a distinct input which are further analyzed through protein interaction analyses. Proteinarium output includes the gene lists of visualized networks and PPI interaction files where users can analyze the network(s) on other platforms such as Cytoscape. In addition, since the dendrogram is written in Newick tree format, users can visualize it in other software platforms like Dendroscope, ITOL.

Conclusions

Proteinarium, through the analysis and visualization of PPI networks, allows researchers to make important observations on high throughput data for a variety of research questions. Proteinarium identifies significant clusters of patients based on their shared network similarity for the disease of interest and the associated genes. Proteinarium is a command-line tool written in Java with no external dependencies and it is freely available athttps://github.com/Armanious/Proteinarium.
DDX3 depletion represses translation of mRNAs with complex 5′ UTRs
Authors: Calviello Lorenzo , Venkataramanan Srivats , Rogowski Karol J. , Wyler Emanuel , Wilkins Kevin , Tejura Malvika , Thai Bao , Krol Jacek , Filipowicz Witold , Landthaler Markus , Floor Stephen N.
Published: March 2019

DDX3 is an RNA chaperone of the DEAD-box family that regulates translation. Ded1, the yeast ortholog of DDX3, is a global regulator of translation, whereas DDX3 is thought to preferentially affect a subset of mRNAs. However, the set of mRNAs that are regulated by DDX3 are unknown, along with the relationship between DDX3 binding and activity. Here, we use ribosome profiling, RNA-seq, and PAR-CLIP to define the set of mRNAs that are regulated by DDX3 in human cells. We find that while DDX3 binds highly expressed mRNAs, depletion of DDX3 particularly affects the translation of a small subset of the transcriptome. We further find that DDX3 binds a site on helix 16 of the human ribosome, placing it immediately adjacent to the mRNA entry channel. Translation changes caused by depleting DDX3 levels or expressing an inactive point mutation are different, consistent with different association of these genetic variant types with disease. Taken together, this work defines the subset of the transcriptome that is responsive to DDX3 inhibition, with relevance for basic biology and disease states where DDX3 is altered.
Multiomics Analysis of the mdx/mTR Mouse Model of Duchenne Muscular Dystrophy
Authors: Van Pelt Douglas W , Kharaz Yalda A , Sarver Dylan C , Eckhardt Logan R , Dzierzawski Justin T , Disser Nathaniel P , Piacentini Alex N , Comerford Eithne , McDonagh Brian , Mendias Christopher L
Published: March 2019

Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease characterized by extensive muscle weakness. Patients with DMD lack a functional dystrophin protein, which transmits force and organizes the cytoskeleton of skeletal muscle. Multiomic studies evaluate combined changes in the transcriptome, proteome, and metabolome, and have been proposed as a way to obtain novel insight about disease processes from preclinical models. We therefore sought to use this approach to study pathological changes in dystrophic muscles. We evaluated hindlimb muscles of male mdx/mTR mice, which lack a functional dystrophin protein and have deficits in satellite cell abundance and proliferative capacity. Wild type (WT) C57BL/6J mice served as controls. Muscle fiber contractility was measured, along with changes in the transcriptome using RNA sequencing, and in the proteome, metabolome, and lipidome using mass spectroscopy. While mdx/mTR mice displayed gross pathological changes and continued cycles of degeneration and regeneration, we found no differences in fiber contractility between strains. However, there were numerous changes in the transcriptome and proteome related to protein balance, contractile elements, extracellular matrix, and metabolism. There was only a 53% agreement in fold change data between the proteome and transcriptome, highlighting the need to study protein abundance along with gene expression measures. Numerous changes in markers of skeletal muscle metabolism were observed, with dystrophic muscles exhibiting elevated glycolytic metabolites. These findings highlight the utility of multiomics in studying muscle disease, and provide additional insight into the pathological changes in dystrophic muscles that might help to guide evidence-based exercise prescription in DMD patients.
Lipid Interactions of a Ciliary Membrane TRP Channel: Simulation and Structural Studies of Polycystin-2 (PC2)
Authors: Wang Qinrui , Hedger George , Aryal Prafulla , Grieben Mariana , Nasrallah Chady , Baronina Agnese , Pike Ashley C.W. , Shi Jiye , Carpenter Elisabeth P. , Sansom Mark S.P.
Published: March 2019

Polycystin-2 (PC2) is a member of the TRPP subfamily of TRP channels and is present in ciliary membranes of the kidney. PC2 can be either homo-tetrameric, or heterotetrameric with PC1. PC2 shares a common transmembrane fold with other TRP channels, in addition to having a novel extracellular domain. Several TRP channels have been suggested to be regulated by lipids, including phosphatidylinositol phosphates (PIPs). We have combined molecular dynamics simulations with cryoelectron microscopy to explore possible lipid interactions sites on PC2. We propose that PC2 has a PIP-binding site close to the equivalent vanilloid/lipid-binding site in the TRPV1 channel. A 3.0 Å cryoelectron microscopy map reveals a binding site for cholesterol on PC2. Cholesterol interactions with the channel at this site are further characterized by MD simulations. These results help to position PC2 within an emerging model of the complex roles of lipids in the regulation and organization of ciliary membranes.
Two forms of phosphomannomutase in gammaproteobacteria: The overlooked membrane-bound form of AlgC is required for twitching motility ofLysobacter enzymogenes
Authors: Qian Guoliang , Fei Shifang , Galperin Michael Y.
Published: March 2019

Lysobacter enzymogenes, a member ofXanthomonadaceae, is a promising tool to control crop-destroying fungal pathogens. One of its key antifungal virulence factors is the type IV pili that are required for twitching motility. Transposon mutagenesis ofL.enzymogenesrevealed that production of type IV pili required the presence of theLe2152gene, which encodes an AlgC-type phosphomannomutase/phosphoglucomutase (PMM). However, in addition to the cytoplasmic PMM domain, the Le2152 gene product contains a ca. 200-aa N-terminal periplasmic domain that is anchored in the membrane by two transmembrane segments and belongs to the dCache superfamily of periplasmic sensor domains. Sequence analysis identified similar membrane-anchored PMMs, encoded in conservedcoaBC-dut-algCgene clusters, in a variety of gammaproteobacteria, either as the sole PMM gene in the entire genome or in addition to the gene encoding the stand-alone enzymatic domain. Previously overlooked N-terminal periplasmic sensor domains were detected in the well-characterized PMMs ofPseudomonas aeruginosaandXanthomonas campestris, albeit not in the enzymes fromPseudomonas fluorescens, Pseudomonas putidaorAzotobacter vinelandii. It appears that after the initial cloning of the enzymatically active soluble part ofP.aeruginosaAlgC in 1991, all subsequent studies utilized N-terminally truncated open reading frames. The N-terminal dCache sensor domain of AlgC is predicted to modulate the PMM activity of the cytoplasmic domain in response to as yet unidentified environmental signal(s). AlgC-like membrane-bound PMMs appear to comprise yet another environmental signaling system that regulates production of type IV pili and potentially other systems in certain gammaproteobacteria.
Acridine form IX
Authors: Stephens Peter W. , Schur Einat , Lapidus Saul H. , Bernstein Joel
Published: March 2019

We report a new polymorph of acridine, C13H9N, denoted form IX, obtained as thin needles by slow evaporation of a toluene solution. The structure was solved and refined from powder X-ray data. The structures of five unsolvated forms were previously known, but this is only the second with one molecule in the asymmetric unit. The melting point [differential scanning calorimetry (DSC) onset] and heat of fusion are 108.8 (3) °C and 19.2 (4) kJ mol−1, respectively.
The crystal structures of two new coumarin derivatives: 2-(4-{2-[(2-oxo-2H-chromen-4-yl)oxy]acetyl}piperazin-1-yl)acetamide and N-(2,4-dimethoxybenzyl)-2-[(2-oxo-2H-chromen-4-yl)oxy]acetamide
Authors: Syed Abuthahir S. , NizamMohideen M. , Viswanathan V. , Govindhan M. , Subramanian K.
Published: March 2019

The title compounds, 2-(4-{2-[(2-oxo-2H-chromen-4-yl)oxy]acetyl}piperazin-1-yl)acetamide, C17H19N3O5, (I), and N-(2,4-dimethoxybenzyl)-2-[(2-oxo-2H-chromen-4-yl)oxy]acetamide, C20H19NO6, (II), are new coumarin derivatives. In compound (I), the six-membered piperazine adopts a chair conformation. The dihedral angles between the mean planes of the chromene ring and amide plane is 82.65 (7)° in (I) and 26.2 (4)° in (II). The dihedral angles between the mean planes of the chromene ring and the four planar C atoms of the piperazine ring in (I) and the benzene ring in (II) are 87.66 (6) and 65.0 (4)°, respectively. There are short intramolecular contacts in both molecules forming S(5) ring motifs, viz. N—H...N and C—H...O in (I), and N—H...O and C—H...N in (II). In the crystals of both compounds, molecules are linked by N—H...O hydrogen bonds, forming chains along [1\overline{1}0] in (I) and [010] in (II). The chains are linked by C—H...O hydrogen bonds, forming layers parallel to the ab plane in the crystals of both compounds. In the crystal of (I), there are also C—H...π and offset π–π interactions [intercentroid distance = 3.691 (1) Å] present within the layers. In the crystal of (II), there are only weak offset π–π interactions [intercentroid distance = 3.981 (6) Å] present within the layers. The intermolecular contacts in the crystals of both compounds have been analysed using Hirshfeld surface analysis and two-dimensional fingerprint plots.
The principle of maṣlaḥah and its application in Islamic banking operations in Malaysia
Authors: Ishak Muhammad Shahrul Ifwat
Published: March 2019

Purpose

This paper aims to investigate the extent to which maṣlaḥah (public interest) is taken into consideration in Islamic banking operations in Malaysia, particularly in bayʿ al-ʿīnah (sale and buyback), taʿwiḍ (compensation) and ibrāʾ (rebate).

Design/methodology/approach

This study applies deductive and inductive methods to analyze the application of maṣlaḥah in Islamic financial transactions. Three issues in Malaysia are selected as a case study, allowing bayʿ al-ʿīnah, standardizing the rate of taʿwiḍ and stipulating the ibrāʾ clause in financial agreements. As this study is qualitative in nature, all data are analyzed based on the content analysis method.

Findings

Both the maṣlaḥah of Islamic banks and their customers were found to be considered by the Central Bank of Malaysia in the implementation of contracts and principles of Islamic banking. The first maṣlaḥah represents the viability of Islamic banks, while the second maṣlaḥah promotes fairness and transparency between Islamic banks and their customers.

Research limitations/implications

This study only focuses on the contracts and principles of Islamic banking operations in Malaysia with regard to three selected issues.

Practical implications

This paper clarifies the practical application of maṣlaḥah in the Islamic banking industry, particularly with regard to implementing its contracts and principles.

Originality/value

This paper analyzes the argument of maṣlaḥah on the issues of bayʿ al-ʿīnah , taʿwiḍ and ibrāʾ in Malaysia, which are considered among scholars to be debatable issues. While many discussions focus on the legal aspect of Sharīʿah on those issues, this study emphasizes how the application of maṣlaḥah aims to solve the current problems and harmonize between Sharīʿah and reality.
Correlates of agrarian indebtedness in rural India
Authors: Surendran Padmaja Subash , Ali Jabir
Published: March 2019

Purpose

The purpose of this paper is to understand the factors determining the incidence and extent of indebtedness among agricultural households in rural India.

Design/methodology/approach

This study is based on a nationally representative survey carried out under the 70th Round of the National Sampling Survey Office (NSSO) across rural India. Data on household characteristics, farming characteristics, indebtedness and extent of outstanding credit have been extracted from the comprehensive survey data. Four research hypotheses have been formulated and tested using simple statistical techniques. Further, using the Heckman Selection Model, the study assesses the factors determining the agrarian indebtedness among households in rural India.

Findings

The results from the descriptive analysis show that there is a significant difference in socio-economic and farm characteristics of indebted and non-indebted households. Further, the level of indebtedness differs across sources of the loan, landholding sizes and geographical locations among agricultural households. The results of regression analysis clearly indicate that household characteristics, farm characteristics and sources of loan determine both the incidence and extent of indebtedness among agricultural households.

Research limitations/implications

The main limitation of the study is that only the data giving information regarding the amount of outstanding loans have been collected, and there is no information regarding the amount of credit availed, the purpose and the due date of payment. Further, there is scope to improve the robustness of the empirical model by adding and modifying explanatory variables.

Originality/value

There are only a limited number of empirical studies providing an understanding of the factors determining the indebtedness of agricultural households in rural India. Hence, this study is a good value addition to the existing literature.
Consumers’ preferences for rice attributes in Cambodia: a choice modeling approach
Authors: Bairagi Subir , Mohanty Samarendu , Custodio Marie Claire
Published: March 2019

Purpose

The purpose of this paper is to examine rice attributes that are valued by the urban consumers of Cambodia and identifies the factors that influence consumers’ decisions on a set of rice attributes.

Design/methodology/approach

The study uses incomplete ranking choice data, gathered from a stated preference survey conducted from 350 consumers of two cities in Cambodia, to model consumers’ alternative choices of rice traits in a setting of a random utility framework. Empirically, a rank-ordered logistic regression is fitted to identify the factors influencing consumers’ perception on a set of rice attributes.

Findings

The results suggest that the probability of choosing rice that is soft is highest for consumers in Cambodia. The second and third most preferred rice attributes are taste and aroma, respectively. The results also indicate that rice consumption is significantly affected by location, economic class of consumers, family size and educational attainment.

Research limitations/implications

The research was carried out using consumers in two urban cities in Cambodia as a case study; therefore, the findings might not represent all consumers’ preferences for rice traits in the country.

Originality/value

The present study contributes to the overall rice grain preference literature examining consumers’ perceptions on rice traits and the factors influencing their decision in choosing rice traits. The results originating from this study will help to guide rice breeders in developing new varieties with traits that will be acceptable to consumers and other value chain actors.
Determinants of innovation
Authors: Restrepo-Morales Jorge Aníbal , Loaiza Osmar Leandro , Vanegas Juan Gabriel
Published: March 2019

Purpose

This paper aims to study the influence of innovation on micro, small and medium-sized enterprises (MSME) performance in Colombia through the 403 MSMES survey analysis. In particular, this paper measures the effect of participation in R&D alliances, product innovation and process innovation on it.

Design/methodology/approach

MSME performance is measured through a composite index, estimated through principal components analysis using polychoric correlations, which is based on eight self-reported assessments of MSME performance. Then, this measure of performance is related to MSME participation in R&D alliances and the product and process development stance of the MSME based on an adaptation of the Miles and Snow business classification scheme, by means of an ANOVA and a linear regression.

Findings

Colombian SMEs are not significantly benefitted from participation on R&D alliances. Instead, their performance appears to be dependent upon their internal innovation efforts directed to product development. Moreover, the results suggest that imitators get a performance almost as high as innovators.

Originality/value

Innovation activities in Colombian SMEs are carried out informally, as they are mostly uninterested to engage in R&D activities and to develop new products by own initiative. Moreover, few of them have an R&D department. In regard to technology, results suggest that almost half of SMEs are classified as followers, namely, they use the same technology as competitors.
The relationship between the income and behavioural biases
Authors: Isidore R. Renu , P. Christie
Published: March 2019

Purpose

The purpose of this paper is to test the relationship between the annual income earned by the investors and eight behavioural biases exhibited by the investors such as mental accounting, anchoring, gambler’s fallacy, availability, loss aversion, regret aversion, representativeness and overconfidence.

Design/methodology/approach

The relationship is derived based on a questionnaire survey conducted on 436 secondary equity investors residing in Chennai, India.

Findings

Analysis of variance test was performed on the normalised and non-normalised version of the biases divided in terms of the annual income earned by the investor. The test found that for the significant biases except the overconfidence bias, the investors with higher annual income were less prone to the biases when compared to investors with lower annual income. On the other hand, with respect to the overconfidence bias, the investors with higher annual income were prone to exhibit overconfidence bias when compared to the investors with lower annual income. Correlation analysis showed that the investors with high annual income were more likely to exhibit higher overconfidence bias but lower representativeness, loss aversion, availability and mental accounting biases.

Originality/value

A contribution in the financial and economic front which would benefit the financial advisors to now consider the income earned by the clients as an important factor while giving financial advice to the clients and while guiding them about the biases they are prone to exhibit.