bluuebunny/crossref_metadata_2025 huggingface dataset:
PCR-based tests for the early diagnosis of sepsis. Where do we stand?
Authors: Ginn Andrew N. , Halliday Catriona L. , Douglas Abby P. , Chen Sharon C-A.
Published: October 2017

Purpose of review

Bloodstream infections are a major cause of hospital and ICU admission with high morbidity and mortality; however, early and targeted antimicrobial therapy reduces mortality in high-risk patients. This article focuses on the diagnosis of bloodstream infections by PCR-based approaches at an early stage to enable prompt treatment and prevent organ dysfunction.

Recent findings

PCR systems offering highly multiplexed targeting of bacterial and/or fungal pathogens (in whole blood) offer the best opportunity for clinical impact, as informed decisions can be made within 4–8 h of the blood draw. Although more rapid, these systems are typically associated with lower sensitivity and specificity than postculture detection methods which rely on microbial growth. Additionally, unlike postculture methods, detection directly from blood is not prone to misleading results because of concurrent (or previous) therapy, which limit clinical relevance.

Rapid and accurate identification of the cause of sepsis is essential in improving patient outcomes. Early identification of these pathogens by nucleic acid detection assays directly from blood samples remains key to achieving this, particularly if taken at the time of presentation. Selection of the most suitable PCR system is typically influenced by local epidemiology and by the resources of the testing laboratory.
Comparison of Unenhanced T1-Weighted Signal Intensities Within the Dentate Nucleus and the Globus Pallidus After Serial Applications of Gadopentetate Dimeglumine Versus Gadobutrol in a Pediatric Population
Authors: Renz Diane M. , Kümpel Stefanie , Böttcher Joachim , Pfeil Alexander , Streitparth Florian , Waginger Matthias , Reichenbach Jürgen R. , Teichgräber Ulf K. , Mentzel Hans-Joachim
Published: October 2017

Objective

The aim of this study was to evaluate and compare changes in T1-weighted signal intensity (SI) within the dentate nucleus (DN) and globus pallidus (GP) in a pediatric population after serial applications of the linear gadolinium-based magnetic resonance contrast medium gadopentetate dimeglumine and the more stable macrocyclic agent gadobutrol.

Materials and Methods

Institutional review board approval was obtained. Two similar pediatric patient cohorts who underwent at least 3 serial contrast-enhanced magnetic resonance imaging (MRI) examinations with sole application of gadopentetate dimeglumine or gadobutrol were analyzed. All MRI examinations were performed on a 1.5 T system acquiring unenhanced T1-weighted spin echo sequences, which were evaluated on the baseline MRI and after the contrast medium administrations. For analysis of SI changes in the DN, the ratios of the DN to the pons (P) and to the middle cerebellar peduncle (MCP) were assessed. The GP was compared with the thalamus (TH) by dividing the SIs between GP and TH (GP-to-TH ratio).

Results

Twenty-eight patients (13 boys, 15 girls; mean age, 8.4 ± 6.8 years) who received at least 3 applications of gadopentetate dimeglumine and 25 patients (13 boys, 12 girls; mean age, 9.7 ± 5.4 years) with 3 or more gadobutrol injections were included. After 3 administrations of gadopentetate dimeglumine, the T1-weighted SI ratios significantly increased: mean difference value of 0.036 ± 0.031 (DN-to-P; P < 0.001), 0.034 ± 0.032 (DN-to-MCP; P < 0.001), and 0.025 ± 0.025 (GP-to-TH; P = 0.001). In a subanalysis of 12 patients with more than 3 injections of gadopentetate dimeglumine, the mean differences of the SI ratios were slightly higher: 0.043 ± 0.032 (DN-to-P; P = 0.001), 0.041 ± 0.035 (DN-to-MCP; P = 0.002), and 0.028 ± 0.025 (GP-to-TH; P = 0.003). In contrast, gadobutrol did not show a significant influence on the SI ratios, neither after 3 nor after more than 3 applications.

Conclusions

The T1-weighted SI increase within the DN and GP after serial administrations of the linear contrast medium gadopentetate dimeglumine, but not after serial applications of the macrocyclic agent gadobutrol, found in a pediatric population, is consistent with results published for adult patients. The clinical impact of the intracranial T1-hyperintensities is currently unclear. However, in accordance with the recent decision of the Pharmacovigilance and Risk Assessment Committee of the European Medicines Agency, intravenous macrocyclic agents should be preferred and MR contrast media should be used with caution and awareness of the pediatric brain development in children and adolescents.
Compressed-Sensing Accelerated 3-Dimensional Magnetic Resonance Cholangiopancreatography
Authors: Zhu Liang , Wu Xi , Sun Zhaoyong , Jin Zhengyu , Weiland Elisabeth , Raithel Esther , Qian Tianyi , Xue Huadan
Published: October 2017

Objectives

The aims of this study were to prospectively evaluate image quality, duct visibility, and diagnostic performance in duct-related pathologies of compressed-sensing (CS) accelerated 3-dimensional (3D) magnetic resonance cholangiopancreatography (MRCP) prototype protocols and compare these with those of conventional 3D MRCP protocol in patients with suspected pancreatic diseases.

Material and Methods

The institutional review board approved this prospective study and all patients provided written informed consent. A total of 80 patients (47 men and 33 women; median age, 57 years; age range, 24–87 years) underwent 3D MRCP at 3.0 T. Three protocols were performed in each patient in random order: CS breath-hold (BH) protocol, CS navigator-triggered (NT) protocol, and conventional NT protocol. The acquisition time of each protocol was recorded. Image quality and duct visibility were independently rated in random order on a 5-point scale by 2 radiologists, who were blinded to the protocols. Receiver operating characteristic curves were generated, and area under the curve (Az value) was used to compare the diagnostic performance of each protocol in duct-related pathologies.

Results

Acquisition time was 17 seconds for the CS-BH and 134.1 ± 33.5 seconds for the CS-NT protocol, both being significantly shorter than the conventional NT protocol (364.7 ± 78.4 seconds; both P < 0.01). The CS-BH MRCP protocol showed significantly less artifacts compared with the CS-NT and conventional NT protocols (both P < 0.01). Visualization of bile ducts was comparable in all 3 protocols, whereas CS-NT and conventional NT MRCP depicted pancreatic duct better than CS-BH MRCP did (for proximal, middle, and distal segment; all P < 0.05). Compressed-sensing-NT MRCP had the highest diagnostic performance for detecting ductal anomalies, long-segment duct stenosis, abnormal branch ducts, and communication between cystic lesion and pancreatic duct (mean Az value, 0.943–0.983).

Conclusions

Compressed-sensing MRCP is feasible in patients with suspected pancreatic diseases. Compressed-sensing-NT MRCP demonstrated superior diagnostic accuracy for duct-related pathologies.
Robotic Versus Laparoscopic Minimally Invasive Surgery for Rectal Cancer
Authors: Prete Francesco Paolo , Pezzolla Angela , Prete Fernando , Testini Mario , Marzaioli Rinaldo , Patriti Alberto , Jimenez-Rodriguez Rosa Maria , Gurrado Angela , Strippoli Giovanni F. M.
Published: October 2017

Objective:

The aim of this study was to evaluate the safety and efficacy of elective rectal resection for rectal cancer in adults by robotic surgery compared with conventional laparoscopic surgery.

Summary of Background Data:

Technological advantages of robotic surgery favor precise dissection in narrow spaces. However, the evidence base driving recommendations for the use of robotic surgery in rectal cancer primarily hinges on observational data.

Methods:

We searched MEDLINE, Embase, and CENTRAL for randomized controlled trials (until August 2016) comparing robotic surgery versus conventional laparoscopic surgery. Data on the following endpoints were evaluated: circumferential margin status, mesorectal grade, number of lymph nodes harvested, rate of conversion to open surgery, postoperative complications, and operative time. Data were summarized as relative risks (RR) or weighted mean differences (WMDs) with 95% confidence intervals (95% CIs). Risk of bias of studies was assessed with standard methods.

Results:

Five trials were eligible, including 334 robotic and 337 laparoscopic surgery cases. Meta-analysis showed that RS was associated with lower conversion rate (7.3%; 4 studies, 544 participants, RR 0.58; 95% CI 0.35–0.97, P = 0.04, I2 = 0%) and longer operating time (MD 38.43 minutes, 95% CI 31.84–45.01: P < 0.00001) compared with laparoscopic surgery. Perioperative mortality, rate of circumferential margin involvement (2 studies, 489 participants, RR 0.82, 95% CI 0.39–1.73), and lymph nodes collected (mean 17.4 Lymph Nodes; 5 trials, 674 patients, MD −0.35, 95% CI −1.83 to 1.12) were similar. The quality of the evidence was moderate for most outcomes.

Conclusion:

Evidence of moderate quality supports that robotic surgery for rectal cancer produces similar perioperative outcomes of oncologic procedure adequacy to conventional laparoscopic surgery. Robotic surgery portraits lower rate of conversion to open surgery, while operating time is significantly longer than by laparoscopic approach.
Endoscopic Treatment of the Zenker Diverticulum With Flexible Endoscopic Myotomy: A Single Tertiary Center Experience
Authors: Dişibeyaz Selçuk , Kuzu Ufuk B. , Parlak Erkan , Saygili Fatih , Öztaş Erkin , Ari Derya , Şahin Burhan
Published: October 2017

Introduction:

The Zenker diverticulum (ZD) is the most common type of esophageal diverticula. Management of ZD has different options; however, there is a recent increase in treatment with flexible endoscopic myotomy (FEM). In our study, we aimed to investigate the efficacy and safety of FEM among patients with ZD.

Materials and Methods:

The data of patients who underwent FEM for ZD in our clinic between January 2008 and May 2016 were retrospectively analyzed. Myotomy was performed with a needle-knife sphincterotome by using pulse-cut or forced coagulation electrocautery mode. Myotomy was performed on the common wall of the diverticulum up to 0.5 to 1 cm of the distal end. A handmade diverticuloscope, which was modified from an overtube, was used in most of the patients to focus more carefully on the septum. Dysphagia scores of the patients before and after the procedure were compared and complications were evaluated.

Results:

A total of 17 patients were enrolled in the study. The mean age was 65.3 years, and mean diverticular diameter was 3.2 cm. The most common symptoms were dysphagia and regurgitation. The mean in-hospital stay was 5 days. The dysphagia score was significantly decreased after FEM among the patients (0.17±0.39 vs. 2±0.79; P=0.0001). Complications were observed in 3 patients (17.6%); however, there was no procedure-related mortality.

Discussion:

FEM is an efficient and safe procedure as a treatment modality for ZD. However, lack of a standard algorithm is a remarkable disadvantage.
Frequency of In-Home Internet Use Among Prekidney and Postkidney Transplant Patients—Facilitators and Barriers to Use and Trends Over Time
Authors: Lockwood Mark B. , Dunn-Lopez Karen , Burke Larisa , Becker Yolanda T. , Saunders Milda
Published: October 2017

Background

As health-related communications become digitized, strategies to increase adoption of these Web-based platforms are needed. The purpose of this study was to assess facilitators and barriers to in-home Internet use among prekidney and postkidney transplant patients.

Methods

A single center, cross-sectional survey of 240 consecutive patients of all levels of technological proficiency who presented to an urban transplant center in the United States. The Patient Information and Technology Assessment consists of 6 demographic questions, 3 disease-related questions, and 8 technology-related questions.

Results

Much of the sample was African American, male with a mean age of 51 years, and median income of $53 800/year. Logistic regression analysis was undertaken, and after adjusting for covariates, we found Smartphone ownership (odds ratio [OR], 4.94; 95% confidence interval [CI], 2.32-10.52), a higher number of Internet users in the home (OR, 2.00; 95% CI, 1.11-3.62), and having college education and beyond (OR, 4.88; 95% CI, 2.03-11.74) increased the likelihood of being a frequent Internet user. African American or Hispanic/Latino patients were less likely to be frequent Internet users compared with white patients (OR, 0.26 and 0.24, respectively, compared with whites, all P < 0.05). As the total number of people in the household increased, frequent Internet use decreased (OR, 0.52; 95% CI, 0.29-0.92). As age increased, reports of frequent Internet use decreased.

Conclusions

Lower rates of Internet use among African Americans and Hispanic/Latinos in urban areas in the United States remains a problem despite a significant increase in access to the Internet and Smartphone ownership. The finding that Internet use increases as the number of Internet users in the household increases indicates that leveraging the patient’s social support network and/or the development of patient information champion programs may aid with patient’s adoption of health technology and patient engagement in self-care.
The Efficacy of Istradefylline for Treating Mild Wearing-Off in Parkinson Disease
Authors: Yabe Ichiro , Kitagawa Mayumi , Takahashi Ikuko , Matsushima Masaaki , Sasaki Hidenao
Published: October 2017

Objectives

The adenosine A2A antagonist istradefylline has been used to treat Parkinson disease (PD) with symptoms of wearing-off since 2013 in Japan. Previous randomized controlled trials of istradefylline compared with placebo included PD patients experiencing an average daily OFF time of more than 2 hours. The purpose of this study is to assess the efficacy of 20 mg/d istradefylline in PD subjects experiencing an average daily OFF time of 3 hours or less.

Methods

Fifteen patients were enrolled into this retrospective study. They received 20 mg/d istradefylline for 12 weeks. Changes in the Unified Parkinson's Disease Rating Scale part III scores in the ON state (ON-UPDRS-III) scores and daily OFF time were assessed at baseline and after 4, 8, and 12 weeks of administration of istradefylline.

Results

At baseline, all subjects had shorter daily OFF times, lower doses of L-DOPA and higher ON-UPDRS-III scores than those in previous randomized controlled trials. Twelve weeks of istradefylline significantly reduced ON-UPDRS-III scores (P < 0.001, Wilcoxon signed rank test). Eleven patients (73%) showed more than 50% reductions in ON-UPDRS-III scores. Improvement of ON-UPDRS-III was significantly correlated with baseline ON-UPDRS-III, and the mean ON-UPDRS-III score at end point was 12.1.

Conclusions

Our result suggests that 20 mg/d istradefylline significantly improved motor functions in PD patients with mild wearing-off.
Electrophysiology of Olfactory and Optic Nerve in Outpatient and Intraoperative Settings
Authors: Hariharan Praveen , Balzer Jeffery R. , Anetakis Katherine , Crammond Donald J. , Thirumala Parthasarathy D.
Published: October 2017

Evoked potentials are time-locked electrophysiologic potentials recorded in response to standardized stimuli using scalp electrodes. These responses provide good temporal resolution and have been used in various clinical and intraoperative settings. Olfactory evoked potentials (OEPs) may be used as an adjunct tool in identifying patients of Parkinson disease and Alzheimer dementia. In clinical practice, visual evoked potentials (VEPs) are particularly useful in identifying subclinical cases of optic neuritis and in treatment surveillance. In recent times, pattern electroretinograms and photopic negative response have been gaining attention in identifying glaucoma suspects. During surgical manipulation, there is a risk of damage to optic or olfactory nerve. Intraoperative neurophysiologic monitoring can provide information regarding the integrity of olfactory or visual pathway. OEPs and VEPs, however, show high degree of variability and are not reliable tools because the responses are extremely susceptible to volatile anesthetic agents. Newer techniques that could possibly circumvent these drawbacks have been developed but are not used extensively. In this article, we briefly review the available techniques to obtain OEPs and VEPs, diagnostic applications, the utility of intraoperative monitoring, the limitations of the current techniques, and the future directions for research.
Quantum-like dynamics applied to cognition: a consideration of available options
Authors: Broekaert Jan , Basieva Irina , Blasiak Pawel , Pothos Emmanuel M.
Published: October 2017

Quantum probability theory (QPT) has provided a novel, rich mathematical framework for cognitive modelling, especially for situations which appear paradoxical from classical perspectives. This work concerns the dynamical aspects of QPT, as relevant to cognitive modelling. We aspire to shed light on how the mind's driving potentials (encoded in Hamiltonian and Lindbladian operators) impact the evolution of a mental state. Some existing QPT cognitive models do employ dynamical aspects when considering how a mental state changes with time, but it is often the case that several simplifying assumptions are introduced. What kind of modelling flexibility does QPT dynamics offer without any simplifying assumptions and is it likely that such flexibility will be relevant in cognitive modelling? We consider a series of nested QPT dynamical models, constructed with a view to accommodate results from a simple, hypothetical experimental paradigm on decision-making. We consider Hamiltonians more complex than the ones which have traditionally been employed with a view to explore the putative explanatory value of this additional complexity. We then proceed to compare simple models with extensions regarding both the initial state (e.g. a mixed state with a specific orthogonal decomposition; a general mixed state) and the dynamics (by introducing Hamiltonians which destroy the separability of the initial structure and by considering an open-system extension). We illustrate the relations between these models mathematically and numerically.

This article is part of the themed issue ‘Second quantum revolution: foundational questions’.
Contextuality in canonical systems of random variables
Authors: Dzhafarov Ehtibar N. , Cervantes Víctor H. , Kujala Janne V.
Published: October 2017

Random variables representing measurements, broadly understood to include any responses to any inputs, form a system in which each of them is uniquely identified by its content (that which it measures) and its context (the conditions under which it is recorded). Two random variables are jointly distributed if and only if they share a context. In a canonical representation of a system, all random variables are binary, and every content-sharing pair of random variables has a unique maximal coupling (the joint distribution imposed on them so that they coincide with maximal possible probability). The system is contextual if these maximal couplings are incompatible with the joint distributions of the context-sharing random variables. We propose to represent any system of measurements in a canonical form and to consider the system contextual if and only if its canonical representation is contextual. As an illustration, we establish a criterion for contextuality of the canonical system consisting of all dichotomizations of a single pair of content-sharing categorical random variables.

This article is part of the themed issue ‘Second quantum revolution: foundational questions’.
Path-sum solution of the Weyl quantum walk in 3 + 1 dimensions
Authors: D'Ariano G. M. , Mosco N. , Perinotti P. , Tosini A.
Published: October 2017

We consider the Weyl quantum walk in 3+1 dimensions, that is a discrete-time walk describing a particle with two internal degrees of freedom moving on a Cayley graph of the group

, which in an appropriate regime evolves according to Weyl's equation. The Weyl quantum walk was recently derived as the unique unitary evolution on a Cayley graph of

that is homogeneous and isotropic. The general solution of the quantum walk evolution is provided here in the position representation, by the analytical expression of the propagator, i.e. transition amplitude from a node of the graph to another node in a finite number of steps. The quantum nature of the walk manifests itself in the interference of the paths on the graph joining the given nodes. The solution is based on the binary encoding of the admissible paths on the graph and on the semigroup structure of the walk transition matrices.

This article is part of the themed issue ‘Second quantum revolution: foundational questions’.
Dual RNAseq shows the human mucosal immunity protein, MUC13, is a hallmark ofPlasmodiumexoerythrocytic infection
Authors: LaMonte Gregory M. , Orjuela-Sanchez Pamela , Wang Lawrence , Li Shangzhong , Swann Justine , Cowell Annie N. , Zou Bing Yu , Abdel-Haleem Mohamed Alyaa M. , Villa-Galarce Zaira , Moreno Marta , Tong-Rios Carlos , Vinetz Joseph M. , Lewis Nathan , Winzeler Elizabeth A.
Published: October 2017

The exoerythrocytic stage ofPlasmodiummalaria infection is a critical window for prophylactic intervention. Using a genome-wide dual RNA sequencing of flow-sorted infected and uninfected hepatoma cells we identify the human mucosal immunity gene,Mucin13 (MUC13), as strongly upregulated duringPlasmodiumexoerythrocytic hepatic-stage infection. We confirm thatMUC13expression is upregulated in hepatoma cell lines and primary hepatocytes. In immunofluorescence assays, host MUC13 protein expression distinguishes infected cells from adjacent uninfected cells and shows similar colocalization with parasite biomarkers such as UIS4 and HSP70. We further show that localization patterns are species independent, distinguishing bothP. bergheiandP. vivaxinfected cells, and that MUC13 can be used to identify compounds that inhibit parasite replication in hepatocytes across all Human-infectingPlasmodiumspecies. This data presents a novel interface of host-parasite interactions inPlasmodium, in that a component of host mucosal immunity is reprogrammed to assist the progression of infection.
OnACID: Online Analysis of Calcium Imaging Data in Real Time*
Authors: Giovannucci Andrea , Friedrich Johannes , Kaufman Matt , Churchland Anne , Chklovskii Dmitri , Paninski Liam , Pnevmatikakis Eftychios A.
Published: October 2017

Optical imaging methods using calcium indicators are critical for monitoring the activity of large neuronal populations in vivo. Imaging experiments typically generate a large amount of data that needs to be processed to extract the activity of the imaged neuronal sources. While deriving such processing algorithms is an active area of research, most existing methods require the processing of large amounts of data at a time, rendering them vulnerable to the volume of the recorded data, and preventing realtime experimental interrogation. Here we introduce OnACID, an Online framework for the Analysis of streaming Calcium Imaging Data, including i) motion artifact correction, ii) neuronal source extraction, and iii) activity denoising and deconvolution. Our approach combines and extends previous work on online dictionary learning and calcium imaging data analysis, to deliver an automated pipeline that can discover and track the activity of hundreds of cells in real time, thereby enabling new types of closed-loop experiments. We apply our algorithm on two large scale experimental datasets, benchmark its performance on manually annotated data, and show that it outperforms a popular offline approach.
Glioma Through the Looking GLASS: the Glioma Longitudinal Analysis consortium, molecular evolution of diffuse gliomas
Authors:   The GLASS consortium, Aldape Kenneth , Amin Samirkumar B , Ashley David M , Barnholtz-Sloan Jill S , Bates Amanda J , Beroukhim Rameen , Bock Christoph , Brat Daniel J , Claus Elizabeth B , Costello Joseph F , de Groot John F , Finocchiaro Gaetano , French Pim J , Gan Hui K , Griffith Brent , Herold-Mende Christel C , Horbinski Craig , Iavarone Antonio , Kalkanis Steven N , Karabatsou Konstantina , Kim Hoon , Kouwenhoven Mathilde CM , McDonald Kerrie L , Miletic Hrvoje , Nam Do-Hyun , Ng Ho Keung , Niclou Simone P , Noushmehr Houtan , Ormond D Ryan , Poisson Laila M , Reifenberger Guido , Roncaroli Federico , Sa Jason K , Sillevis Smitt Peter AE , Smits Marion , Souza Camila F , Tabatabai Ghazaleh , Van Meir Erwin G , Verhaak Roel GW , Watts Colin , Wesseling Pieter , Woehrer Adelheid , Yung WK Alfred , Jungk Christine , Hau Ann-Christin , Dyck Eric van , Westerman Bart A , Yin Julia , Abiola Olajide , Khasraw Mustafa , Sulman Erik P , Muscat Andrea M
Published: October 2017

Adult diffuse glioma are a diverse group of intracranial neoplasms associated with a disproportional large number of productive life years lost, thus imposing a highly emotional and significant financial burden on society. Patient death is the result of an aggressive course of disease following diagnosis. The Cancer Genome Atlas and similar projects have provided a comprehensive understanding of the somatic alterations and molecular subtypes of glioma at diagnosis. However, gliomas undergo significant molecular evolution during the malignant transformation. We review current knowledge on genomic, epigenomic and transcriptomic abnormalities before and after disease recurrence. We outline an effort to systemically catalogue the longitudinal changes in gliomas, the Glioma Longitudinal Analysis Consortium. The GLASS initiative will provide essential insights into the evolution of glioma towards a lethal phenotype with the potential to reveal targetable vulnerabilities, and ultimately, improved outcomes for a patient population in need.
Magnetic resonance imaging does not reveal structural alterations in the brain of synesthetes
Authors: Dojat M. , Pizzagalli F. , Hupé JM
Published: October 2017

Several publications have reported structural changes in the brain of synesthetes compared to controls, either local differences or differences in connectivity. In the present study, we pursued this quest for structural brain differences that might support the subjective experience of synaesthesia. In particular, for the first time in this field, we investigated brain folding in comparing 45 sulcal shapes in each hemisphere of control and grapheme-color synesthete populations. To overcome flaws relative to data interpretation based only on p-values, common in the synesthesia literature, we report confidence intervals of effect sizes. Moreover, our statistical maps are displayed without introducing the classical, but misleading, p-value level threshold. We adopt such a methodological procedure to facilitate appropriate data interpretation and promote the New Statistics approach. Based on structural or diffusion magnetic resonance imaging data, we did not find any strong cerebral anomaly, in sulci, tissue volume, tissue density or fiber organization that could support synesthetic color experience. Finally, by sharing our complete datasets, we strongly support the multi-center construction of a sufficient large dataset repository for detecting, if any, subtle brain differences that may help understanding how a subjective experience, such as synesthesia, is mentally constructed.
Biased gene retention in the face of massive nuclear introgression obscures species relationships
Authors: Forsythe Evan S. , Nelson Andrew D. L. , Beilstein Mark A.
Published: October 2017

Phylogenomic analyses are recovering previously hidden histories of hybridization, revealing the genomic consequences of these events on the architecture of extant genomes. We exploit a suite of genomic resources to show that introgressive hybridization occurred between close relatives of Arabidopsis, impacting our understanding of species relationships in the group. The composition of introgressed and retained genes indicates that selection against incompatible cytonuclear and nuclear-nuclear interactions likely acted during introgression, while neutral processes also contributed to genome composition through the retention of ancient haplotype blocks. We also developed a divergence-based test to distinguish donor from recipient lineages without the requirement of additional taxon-sampling. Finally, to our great surprise, we find that cytonuclear discordance appears to have arisen via extensive nuclear, rather than cytoplasmic, introgression, meaning that most of the genome was displaced during introgression, while only a small proportion of native alleles were retained.
Timing of gene expression in a cell-fate decision system
Authors: Aymoz Delphine , Solé Carme , Pierre Jean-Jerrold , Schmitt Marta , de Nadal Eulàlia , Posas Francesc , Pelet Serge
Published: October 2017

During development, morphogens provide extracellular cues allowing cells to select a specific fate by inducing complex transcriptional programs. The mating pathway in budding yeast offers simplified settings to understand this process. Pheromone secreted by the mating partner triggers the activity of a MAPK pathway, which results in the expression of hundreds of genes. Using a dynamic expression reporter, we quantified the kinetics of gene expression in single cells upon exogenous pheromone stimulation and in the physiological context of mating. In both conditions, we observed striking differences in the timing of induction of mating-responsive promoters. Biochemical analyses and generation of synthetic promoter variants demonstrated how the interplay between transcription factor binding and nucleosomes contribute to determine the kinetics of transcription in a simplified cell-fate decision system.

One Sentence Summary

Quantitative and dynamic single cell measurements in the yeast mating pathway uncover a complex temporal orchestration of gene expression events.
Neuropathic mutations in MORC2 perturb GHKL ATPase dimerization dynamics and epigenetic silencing by multiple structural mechanisms
Authors: Douse Christopher H. , Bloor Stuart , Liu Yangci , Shamin Maria , Tchasovnikarova Iva A. , Timms Richard T. , Lehner Paul J. , Modis Yorgo
Published: October 2017

Missense mutations inMORC2cause neuropathies including spinal muscular atrophy and Charcot-Marie-Tooth disease. We recently identified MORC2 as an effector of epigenetic silencing by the HUSH complex. Here we report the biochemical and cellular activities of MORC2 variants, alongside crystal structures of wild-type and neuropathic forms of a human MORC2 fragment comprising the GHKL-type ATPase module and CW-type zinc finger. This fragment dimerizes upon binding ATP and contains a hinged, functionally critical coiled coil insertion absent in other GHKL ATPases. We find that dimerization and DNA binding of the MORC2 ATPase module transduce HUSH-dependent silencing. Disease mutations change the dynamics of dimerization by distinct structural mechanisms: destabilizing the ATPase-CW module, trapping the ATP lid or perturbing the dimer interface. These defects lead to modulation of HUSH function, thus providing a molecular basis for understanding MORC2-associated neuropathies.
Initiation, elongation and realignment during influenza virus mRNA synthesis
Authors: te Velthuis Aartjan J.W. , Oymans Judith
Published: October 2017

The RNA-dependent RNA polymerase (RdRp) of the influenza A virus replicates and transcribes the viral genome segments in the nucleus of the host cell. To transcribe these viral genome segments, the RdRp ‘snatches’ capped RNA oligonucleotides from nascent host cell mRNAs and aligns these primers to the ultimate or penultimate nucleotide of the segments for the initiation of viral mRNA synthesis. It has been proposed that this initiation process is not processive and that the RdRp uses a prime-realign mechanism during transcription. Here we providein vitroevidence for the existence of this transcriptional prime-realign mechanism, but show that it only functions efficiently for primers that are short or can not stably base pair with the template. In addition, we demonstrate that transcriptional elongation is dependent on the priming loop of the PB1 subunit of the RdRp. We propose that the prime-realign mechanism may be used to rescue abortive transcription initiation events or cope with sequence variation among primers. Overall, these observations advance our mechanistic understanding of how the influenza A virus initiates transcription correctly and efficiently.

Importance

The influenza A virus causes severe disease in humans and is considered a major global health threat. The virus replicates and transcribes its genome using an enzyme called the RNA polymerase. To ensure that the genome is amplified faithfully and abundant viral mRNAs are made for viral protein synthesis, the viral RNA polymerase must transcribe the viral genome efficiently. In this report, we characterise a structure inside the polymerase that contributes to the efficiency of viral mRNA synthesis.
The dynamic evolution of Drosophila innubila Nudivirus
Authors: Hill Tom , Unckless Robert
Published: October 2017

Viruses coevolve with their hosts to overcome host resistance and gain the upper hand in the evolutionary arms race. Drosophila innubila nudivirus (DiNV) is a double stranded DNA virus, closely related to Oryctes rhinoceros nudivirus (OrNV) and Kallithea virus. DiNV is the first DNA virus found to naturally infect Drosophila and therefore has the potential to be developed as a model for DNA virus immune defense and host/virus coevolution within its well-studied host system. Here we sequence and annotate the genome of DiNV and identify signatures of adaptation, revealing clues for genes involved in host-parasite coevolution. The genome is 155555bp long and contains 107 coding open reading frames (ORFs) and a wealth of AT-rich simple sequence repeats. While synteny is highly conserved between DiNV and Kallithea virus, it drops off rapidly as sequences become more divergent, consistent with rampant rearrangements across nudiviruses. Overall, we show that evolution of DiNV is likely due to adaptation of few genes coupled with high gene turnover.
C3D: A tool to predict 3D genomic interactions between cis-regulatory elements
Authors: Mehdi Tahmid , Bailey Swneke D. , Guilhamon Paul , Lupien Mathieu
Published: October 2017

Motivation

The 3D genome architecture influences the regulation of genes by facilitating chromatin interactions between distal cis-regulatory elements and gene promoters. We implement Cross Cell-type Correlation based on DNA accessibility (C3D), a highly customizable computational tool that predicts chromatin interactions using an unsupervised algorithm that utilizes correlations in chromatin measurements, such as DNaseI hypersensitivity signals.

Results

C3D accurately predicts 32.7%, 18.3% and 24.1% of interactions, validated by ChIA-PET assays, between promoters and distal regions that overlie DNaseI hypersensitive sites in K562, MCF-7 and GM12878 cells, respectively.

Availability

Source code is open-source and freely available on GitHub (https://github.com/LupienLabOrganization/C3D) under the GNU GPLv3 license. C3D is implemented in Bash and R; it runs on any platform with Bash (≥4.0), R (≥3.1.1) and BEDTools (≥2.19.0). It requires the following R packages: GenomicRanges, Sushi, data.table, preprocessCore and dynamicTreeCut.
Genetic Analysis of Deep Phenotyping Projects in Common Disorders
Authors: Gershon Elliot S. , Pearlson Godfrey , Keshavan Matcheri S. , Tamminga Carol , Clementz Brett , Buckley Peter F. , Alliey-Rodriguez Ney , Liu Chunyu , Sweeney John A. , Keedy Sarah , Meda Shashwath , Tandon Neeraj , Shafee Rebecca , Bishop Jeffrey R. , Ivleva Elena I.
Published: October 2017

Several studies of complex psychotic disorders with large numbers of neurobiological phenotypes are currently under way, in living patients and controls, and on assemblies of brain specimens. Genetic analyses of such data typically present challenges, because of the choice of underlying hypotheses on genetic architecture of the studied disorders and phenotypes, large numbers of phenotypes, the appropriate multiple testing corrections, limited numbers of subjects, imputations required on missing phenotypes and genotypes, and the cross-disciplinary nature of the phenotype measures. Advances in genotype and phenotype imputation, and in genome-wide association (GWAS) methods, are useful in dealing with these challenges. As compared with the more traditional single-trait analyses, deep phenotyping with simultaneous genome-wide analyses serves as a discovery tool for previously unsuspected relationships of phenotypic traits with each other, and with specific molecular involvements.
Genetic reagents for making split-GAL4 lines in Drosophila
Authors: Dionne Heather , Hibbard Karen L. , Cavallaro Amanda , Kao Jui-Chun , Rubin Gerald M.
Published: October 2017

The ability to reproducibly target expression of transgenes to small, defined subsets of cells is a key experimental tool for understanding many biological processes. The Drosophila nervous system contains thousands of distinct cell types and it has generally not been possible to limit expression to one or a few cell types when using a single segment of genomic DNA as an enhancer to drive expression. Intersectional methods, in which expression of the transgene only occurs where two different enhancers overlap in their expression patterns, can be used to achieve the desired specificity. This report describes a set of over 2,800 transgenic lines for use with the split-GAL4 intersectional method.
Methods in field chronobiology
Authors: Dominoni Davide , Åkesson Susanne , Klaassen Raymond , Spoelstra Kamiel , Bulla Martin
Published: October 2017

Chronobiological research has seen a continuous development of novel approaches and techniques to measure rhythmicity at different levels of biological organization from locomotor activity (e.g. migratory restlessness) to physiology (e.g. temperature and hormone rhythms, and relatively recently also in genes, proteins and metabolites). However, the methodological advancements in this field have been mostly and sometimes exclusively used only in indoor laboratory settings. In parallel, there has been an unprecedented and rapid improvement in our ability to track animals and their behaviour in the wild. However, while the spatial analysis of tracking data is widespread, its temporal aspect is largely unexplored. Here, we review the tools that are available or have potential to record rhythms in the wild animals with emphasis on currently overlooked approaches and monitoring systems. We then demonstrate, in three question-driven case studies, how the integration of traditional and newer approaches can help answer novel chronobiological questions in free-living animals. Finally, we highlight unresolved issues in field chronobiology that may benefit from technological development in the future. As most of the studies in the field are descriptive, the future challenge lies in applying the diverse technologies to experimental set-ups in the wild.
Thalamostriatal and cerebellothalamic pathways in a songbird, the Bengalese finch
Authors: Nicholson David A. , Roberts Todd , Sober Samuel J.
Published: October 2017

The thalamostriatal system is a major network in the mammalian brain, originating principally from the intralaminar nuclei of thalamus. Functions of the thalamostriatal system remain unclear, but a subset of these projections provides a pathway through which the cerebellum communicates with the basal ganglia. Both the cerebellum and basal ganglia play crucial roles in motor control. Although songbirds have yielded key insights into the neural basis of vocal learning, it is unknown whether a thalamostriatal system exists in the songbird brain. Thalamic nucleus DLM is an important part of the song system, the network of nuclei required for learning and producing song. DLM receives output from song system basal ganglia nucleus Area X and sits within dorsal thalamus, the proposed avian homolog of the mammalian intralaminar nuclei that also receives projections from the cerebellar nuclei. Using a viral vector that specifically labels presynaptic axon segments, we show in Bengalese finches that dorsal thalamus projects to Area X, the basal ganglia nucleus of the song system, and to surrounding medial striatum. To identify the sources of thalamic input to Area X, we map DLM and cerebellar-recipient dorsal thalamus (DTCbN). Surprisingly, we find both DLM and immediately-adjacent subregions of DTCbN project to Area X. In contrast, a medial-ventral subregion of DTCbN projects to medial striatum outside Area X. Our results suggest the basal ganglia in the song system, like the mammalian basal ganglia, integrate feedback from the thalamic region to which they project as well as thalamic regions that receive cerebellar output.
Integrating piggyBac Transposon Transgenes into Mouse Fibroblasts Using Chemical Methods
Authors: Behringer Richard , Gertsenstein Marina , Nagy Kristina Vintersten , Nagy Andras
Published: October 2017

Mouse embryonic fibroblasts can be reprogrammed to ES cell-like pluripotent stem cells by the forced expression of four transcription factors—OCT4, SOX2, KLF4, and c-MYC. The piggyBac transposon system has proven effective as a vehicle for the delivery of transgenes into fibroblasts and for successful reprogramming to induced pluripotent stem (iPS) cells. We found that FuGENE HD transfection reagent can be effective for mouse embryonic fibroblasts (MEFs) to generate induced pluripotent stem cells (iPSCs) with the piggyBac transposon transgenes. There are multitudes of cell transfection methods commercially available. Their efficiency, and thus their success, in inducing pluripotent cell types are cell-type-dependent.
Spear phishing in organisations explained
Authors: Bullee Jan-Willem , Montoya Lorena , Junger Marianne , Hartel Pieter
Published: October 2017

Purpose

The purpose of this study is to explore how the opening phrase of a phishing email influences the action taken by the recipient.

Design/methodology/approach

Two types of phishing emails were sent to 593 employees, who were asked to provide personally identifiable information (PII). A personalised spear phishing email opening was randomly used in half of the emails.

Findings

Nineteen per cent of the employees provided their PII in a general phishing email, compared to 29 per cent in the spear phishing condition. Employees having a high power distance cultural background were more likely to provide their PII, compared to those with a low one. There was no effect of age on providing the PII requested when the recipient’s years of service within the organisation is taken into account.

Practical implications

This research shows that success is higher when the opening sentence of a phishing email is personalised. The resulting model explains victimisation by phishing emails well, and it would allow practitioners to focus awareness campaigns to maximise their effect.

Originality/value

The innovative aspect relates to explaining spear phishing using four socio-demographic variables.
Universal social pension for elderly individuals in India
Authors: Muttur Ranganathan Narayana
Published: October 2017

Purpose

Population ageing, extended coverage of beneficiaries and rise in benefit levels of a public-funded universal social pension scheme (USPS) for elderly individuals may exert fiscal pressures on India’s General Government. Using accounting frameworks, this paper aims at an assessment of public expenditure requirements of USPS scenarios in the short term and their long-term implications for fiscal sustainability.

Design/methodology/approach

Short-term public expenditure requirements are quantified for the current pension scheme and proposed USPS scenarios, if pension benefits are adjustable for official poverty line, per capita income, the inflation rate and income elasticity of public pension expenditure. Long-term fiscal sustainability is determined by the methodology of generational accounting.

Findings

Public expenditure requirements for the USPS scenarios are remarkably higher as compared to the current expenditure on the Indira Gandhi National Old Age Pension Scheme (IGNOAPS). Short-term analyses offer economic justifications for an increase in pension benefits either by a single adjustment factor or combined adjustment factors but at a cost of remarkable increase in public expenditure requirements. Long-term analyses show that the IGNOAPS and proposed USPS scenarios are fiscally sustainable but sensitive to five parameters (productivity growth, inflation rate, discount rate, income elasticity public pension expenditure and income elasticity of health expenditure). A policy mix of these parameters leads to fiscal sustainability of the IGNOAPS and proposed USPS scenarios with differential impacts on inter-generational distribution of welfare by tax and transfer adjustments.

Research limitations/implications

Application of the generational accounting methodology is new for India’s pension economics and may have applicability and relevance for future extensions and analyses of other fiscal policy issues. This paper sets a benchmark for such extensions and applications.

Practical implications

The analyses and implications offer economic justifications for increase in levels of pension benefits by the current pension scheme and proposed USPS scenarios, introduction of sustainable USPS scenarios under current fiscal policies and choice of design parameters for a fiscally sustainable USPS.

Social implications

Social pensions have implications for providing income security and livelihood benefits for all elderly civilians in society.

Originality/value

The paper adds to the existing knowledge on economic analyses and fiscal implications of India’s old age pension policies in general and social pension policies in particular. Subject to the comparability of socio-economic structures and pension programmes, the methodology and public policy analyses of this paper may be of relevance and applicability for developing countries in Asia.
An empirical investigation of perceived relational benefits and brand engagement in restaurant services
Authors: Odoom Raphael , Boateng Henry , Asante Bismark Omane
Published: October 2017

Purpose

The paper aims to examine the nexus between perceived relational benefits and brand engagement within a restaurant setting in a developing economy context.

Design/methodology/approach

This paper used a survey research design, obtaining data via self-administered questionnaire from 500 customers of 25 restaurants. A five-stage analysis involving exploratory factor analysis, ANOVA, multiple regression, cluster analysis and multinomial logistic regression was carried out using SPSS 22 for Windows.

Findings

Results from the study show that three relational benefits (social benefit, exploration and entertainment) contribute significantly to consumers’ brand engagement in a restaurant service setting. Variations across consumers with low, medium and high brand engagement levels are also provided.

Originality/value

The paper extends the current understanding of brand engagement from a restaurant setting. It provides evidence to issues of potential research and managerial interests and offers insightful implications to the academic and practitioner communities.