bluuebunny/crossref_metadata_2025 huggingface dataset:
Tubo-Ovarian Transitional Cell Carcinoma and High-grade Serous Carcinoma Show Subtly Different Immunohistochemistry Profiles
Authors: Magrill Jamie , Karnezis Anthony N. , Tessier-Cloutier Basile , Talhouk Aline , Kommoss Stefan , Cochrane Dawn , Chow Christine , Cheng Angela , Soslow Robert , Hauptmann Steffen , du Bois Andreas , Pfisterer Jacobus , Gilks C. Blake , Huntsman David G. , Kommoss Friedrich
Published: July 2018

Tubo-ovarian transitional cell carcinoma (TCC) is grouped with high-grade serous carcinoma (HGSC) in the current World Health Organization classification. TCC is associated with BRCA mutations and a better prognosis compared with HGSC. Previous papers examining the immunohistochemical features of TCC have studied limited numbers of samples. No marker reflecting the biological difference between TCC and HGSC is known. We collected a large cohort of TCC to determine whether TCC and HGSC could be distinguished by immunohistochemistry. A tissue microarray was built from 89 TCC and a control cohort of 232 conventional HGSC. Immunohistochemistry was performed, scored, and statistically analyzed for routine markers of HGSC and urothelial tumors: PAX8, WT1, p53, p16, ER, p63, and GATA3. Using scoring cutoffs commonly employed in clinical practice, the immunohistochemical profile of TCC was indistinguishable from HGSC for all markers. However, more detailed scoring criteria revealed statistically significant differences between the 2 groups of tumors with respect to ER, PAX8, and WT1. HGSC showed more diffuse and intense staining for PAX8 (P=0.004 and 0.001, respectively) and WT1 (P=0.002 and 0.002, respectively); conversely, TCC showed more intense staining for ER (P=0.007). TCC and HGSC therefore show subtle differences in their immunohistochemical profiles which might reflect underlying (epi)genetic differences. Further studies using proteomic analysis will focus on the identification of differentially expressed proteins that might serve as markers of TCC-like differentiation, which could help explain biologic differences between TCC and HGSC and might identify other cases of HGSC with a better prognosis.
GATA3 Expression in Common Gynecologic Carcinomas: A Potential Pitfall
Authors: Terzic Tatjana , Mills Anne M. , Zadeh Sarah , Atkins Kristen A. , Hanley Krisztina Z.
Published: July 2018

GATA binding protein 3 (GATA3) immunohistochemistry is primarily used as a marker of breast and urothelial differentiation, particularly in metastatic settings. In the gynecologic tract it also serves a robust marker for mesonephric and trophoblastic tumors. However, expression has also been described in more common malignancies of gynecologic tract including ovarian, endometrial, and cervical carcinomas. Data on the distribution of GATA3 expression in gynecologic malignancies is somewhat limited, particularly across different histologic subtypes of ovarian, endometrial, and cervical carcinomas. To assess the rates of GATA3 expression among common gynecologic cancers of various histologic types, 100 ovarian carcinomas, 64 endometrial carcinomas/atypical hyperplasias, 16 cervical squamous cell carcinomas (SCCs), and 14 endocervical adenocarcinomas were evaluated by immunohistochemistry for GATA3 positivity. Eight percent of endometrial carcinomas expressed GATA3, including 2 serous carcinomas, 1 carcinosarcoma, and 1 case of atypical hyperplasia. Six percent of ovarian carcinomas were GATA3-positive including 2 clear cell carcinomas, 2 mucinous adenocarcinomas, and 2 high-grade serous carcinomas. Thirty-eight percent of cervical SCCs showed weak to moderate staining in up to 50% of tumor cells. All endocervical adenocarcinomas were entirely negative for GATA3. In summary, GATA3 shows focal weak to moderate expression in a subset of endometrial and ovarian carcinomas. In contrast, usual-type endocervical adenocarcinomas are typically negative for GATA3, which can be helpful in differentiating them from mesonephric proliferations or carcinomas. A larger proportion of cervical SCCs express GATA3, therefore caution should be exercised when using this stain in the setting of a lower genitourinary carcinomas.
Content validation of a Critical Appraisal Tool for Reviewing Analgesia Studies (CATRAS) involving subjects incapable of self-reporting pain
Authors: Warne Leon N. , Schug Stephan A. , Beths Thierry , Brondani Juliana T. , Carter Jennifer E. , Lascelles B. Duncan X. , Raisis Anthea L. , Robertson Sheilah A. , Steagall Paulo V.M. , Taylor Polly M. , Whittem Ted , Bauquier Sébastien H.
Published: July 2018

Introduction:

This article reports the content validation of a Critical Appraisal Tool designed to Review the quality of Analgesia Studies (CATRAS) involving subjects incapable of self-reporting pain and provide guidance as to the strengths and weakness of findings. The CATRAS quality items encompass 3 domains: level of evidence, methodological soundness, and grading of the pain assessment tool.

Objectives:

To validate a critical appraisal tool for reviewing analgesia studies involving subjects incapable of self-reporting pain.

Methods:

Content validation was achieved using Delphi methodology through panel consensus. A panel of 6 experts reviewed the CATRAS in 3 rounds and quantitatively rated the relevance of the instrument and each of its quality items to their respective domains.

Results:

Content validation was achieved for each item of the CATRAS and the tool as a whole. Item-level content validity index and kappa coefficient were at least greater than 0.83 and 0.81, respectively, for all items except for one item in domain 2 that was later removed. Scale-level content validity index was 97% (excellent content validity).

Conclusions:

This 67-item critical appraisal tool may enable critical and quantitative assessment of the quality of individual analgesia trials involving subjects incapable of self-reporting pain for use in systematic reviews and meta-analysis studies.
Dual-Energy Computed Tomography Applications in Neurointervention
Authors: Wolman Dylan N. , Patel Bhavik P. , Wintermark Max , Heit Jeremy J.
Published: July 2018

Dual-energy computed tomography (CT) combines the high spatial resolution of standard CT with the ability to improve contrast resolution, reduce artifact, and separate materials of different atomic weights and energy-based attenuation through postprocessing. We review the underlying physical principles and applications of dual-energy CT within the context of patients undergoing preprocedural and postprocedural evaluation for neurointerventional therapies. The broad imaging categories of cerebral ischemia and hemorrhage, head and neck angiography, and the spine are reviewed.
Introduction of Meglumine Diatrizoate into the Middle Cranial Fossa: A Rare Fatal Complication of Temporomandibular Joint Arthrography
Authors: Li Wei , Wei Lili , Wang Fang , Cheng Yong , Li Bo
Published: July 2018

The authors here report a rare fatal complication of temporomandibular joint (TMJ) arthrography. A 57-year-old woman suddenly exhibited spasm and dizziness during TMJ arthrography. A multislice CT scanning of head demonstrated a defect in the roof of the glenoid fossa and unanticipated introduction of meglumine diatrizoate into the middle cranial fossa, which should account for neurotoxic symptoms of the patient and could be fatal if not appropriately treated in time. As TMJ puncture is widely performed in clinical practice and generally considered a safe technique, this case might serve as a reminder of the potential risk of the anatomical variation—a defect in the roof of the glenoid fossa—to TMJ clinical practitioners.
The Nonsurgical Management of Orbital Dystopia Using Refractive Lenses and Prosthetic Shells
Authors: Joganathan Varajini , Terry Patsy , Wall Steve , Norris Jonathan H.
Published: July 2018

Surgical rehabilitation of orbital dystopia can be challenging. The authors demonstrate the effective use of spectacle lenses to visually correct misalignments of the globe and the orbit. Presented is a retrospective review of 4 patients undergoing aesthetic rehabilitation through use of spectacle lenses and in a number patients a cosmetic shell.

Two patients with neurofibromatosis presented with inferior dystopia of the globe and orbit. A base-down prismatic lens applied to the spectacles in conjunction with a prosthetic shell successfully visually corrected the facial asymmetry and improved patients’ aesthetic appearance. One patient with a history of traumatic retinal detachment, who did not want any surgical intervention, a “plus” (hypermetropic) lens was used to magnify the perceived image of an enophthalmic and phthisical globe, to enhance appearance and improve symmetry. In the fourth patient, with Goldenhar syndrome, the appearance of a hypotropia and concurrent esotropia was successfully treated with a Fresnel prism and a prosthetic shell.

This case series illustrates the successful role of various refractive lenses often in conjunction with prosthetic shells in patients with reduced vision and orbital dystopia to improve facial symmetry. This conservative treatment is especially useful when surgery is not a desired or not considered a suitable option for the patient.
Long-term Pelvic Floor Symptoms, Recurrence, Satisfaction, and Regret Following Colpocleisis
Authors: Winkelman William D. , Haviland Miriam J. , Elkadry Eman A.
Published: July 2018

Objectives

There are insufficient studies on long-term outcomes following colpocleisis, which limits physicians' ability to effectively counsel patients. The purpose of this study was to assess pelvic floor symptoms, recurrence, satisfaction, and regret among patients who underwent colpocleisis procedures.

Methods

This is an ambidirectional cohort study involving patients who underwent a colpocleisis at a single institution from 2002 to 2012. Medical records were reviewed, and patients were contacted by telephone in order to complete questionnaires.

Results

A total of 73 patients met inclusion criteria for our study. At the time of colpocleisis, patients were an average of 78.1 years old (range, 62–85 years). Patients were followed up in clinic for a median of 44.4 months, and the majority reported overactive bladder postoperatively. We were able to contact 33 patients by telephone. Median time between surgery and telephone follow-up was 6 years (range, 5–15 years). Among these patients, 78% were satisfied with the procedure; however, 13% reported strong feelings of regret. Regret was associated with postoperative bowel and bladder symptoms. The majority reported urinary frequency (63%) and urgency urinary incontinence (56%). Fewer than half (44%) of patients reported bowel symptoms. Only 19% reported prolapse symptoms. No patients reported regret due to loss of sexual function.

Conclusions

Colpocleisis remains an excellent surgical option for elderly patients. However, regret and dissatisfaction may increase over time as bowel and bladder symptoms may be perceived to be the result of surgery. Our findings highlight the continued need for detailed consent and expectation setting for women considering colpocleisis.
Guiding Principles and Essential Practices of Listening and Spoken Language Intervention in the School-Age Years
Authors: Soman Uma , Nevins Mary Ellen
Published: July 2018

Listening and spoken language (LSL) intervention and education have emerged as the preferred terms representing an intervention perspective that promotes “auditory oral” outcomes for many of today's children who are deaf or hard of hearing (D/HH), including those who are English learners. Practitioners (including speech–language pathologists, educational audiologists, and teachers) working with students who are D/HH require access to evidence-based principles of LSL. A deep understanding of general principles will inform practitioners' development of intervention to promote outcomes for school-aged students who are D/HH or D/HH and English learners. The purpose of this article is to identify principles and practices foundational to developing LSL. Knowledge, skills, and dispositions for practitioners are discussed; descriptions and examples of strategies and resources associated with LSL are included.
Tibial Plateau Fractures
Authors: Ramponi Denise R. , McSwigan Tara
Published: July 2018

Tibial plateau fractures can result from direct trauma or indirect compressive forces. These injuries often result in significant soft tissue disruption, ligamentous disturbance in addition to bone fractures. Diagnostic imaging findings in plain radiographs include fat-fluid level in the suprapatellar bursa, malalignment of the femoral condyles and tibial edges, and increased trabecular density in the lateral epicondyle. Patients in whom a tibial plateau fracture is suspected with negative radiographs should have computerized tomography imaging performed. Most patients will require surgical intervention for fracture fixations. Primary long-term complication includes posttraumatic osteoarthritis because of the traumatic stress forces across the joint.
Outpatient Treatment of Uncomplicated Urinary Tract Infections in the Emergency Department
Authors: Schutz Douglas , Watson Simon C. , Hayden Geoffrey , Weant Kyle A.
Published: July 2018

One of the most commonly treated infections in the emergency department (ED) is an uncomplicated urinary tract infection. Multiple classes of antibiotics are frequently used to treat this condition, but not all have equivalent efficacy, and many may confer risks to not only the patient but society as a whole if used on a large scale. These antibiotic selections should also be guided by local antimicrobial susceptibility patterns, and general multidisciplinary recommendations for therapy should be developed on a local scale to assist prescribing patterns. The proactive development of a routine approach to reviewing and addressing positive cultures following discharge from the ED should also be developed and implemented in order to ensure that optimal patient care is provided. The objective of this review is to assess the available literature to isolate which antibiotics and approaches to care are the most appropriate options for treating uncomplicated outpatient urinary tract infections in the ED.
Implementation of a Smoking Cessation Education Program in the Emergency Department
Authors: González Juan M. , de Tantillo Lila , Snowden Kenya , Gattamorta Karina , Ortega Johis
Published: July 2018

Tobacco use is a major threat to public health. Current guidelines suggest that healthcare professionals in the emergency department provide routine smoking cessation screening and interventions. Evidence suggests that an educational intervention among registered nurses in the emergency department may increase education and referral for smoking cessation of patients who use tobacco products. An educational module regarding smoking cessation counseling was provided to registered nurses in the emergency department at a private hospital in South Florida. A pre- and postintervention self-reported survey evaluated changes in nurses asking about tobacco use; advising to quit; assessing readiness, assisting, and arranging follow-up for patients who smoke to quit; and encouraging pharmacological agents. All participating nurses screened for tobacco use most of the time before and after the intervention. However, the number of nurses who assessed readiness, assisted, arranged follow-up for patients and encouraged the use of pharmacological agents increased significantly in the postsurvey. Study findings agree with previous research indicating that nurses routinely screen for tobacco and advise to quit. However, implementing smoking cessation education and referral resources may better equip registered nurses in the emergency department to take an active role initiating follow-up interventions for patients who screen positive for tobacco use. Educational interventions among these nurses can increase knowledge of and utilization of existing resources to help patients quit.
Synthesis of Research Articles to Examine Reporting of the Educational Preparation and Practice Parameters of Emergency Nurse Practitioners
Authors: Smith Gloria I. , Hodgins Marilyn J.
Published: July 2018

It has been reported that the outcomes of care are affected not only by the educational preparation and experience of the practitioner but also by the parameters of his or her practice. Given differences that exist internationally in the enactment of the emergency nurse practitioner (ENP) role, a synthesis of research articles was conducted to examine the educational preparation and experience of ENPs, the role(s) they assume as determined by their patient population, and the outcomes used to evaluate their practice. The synthesis was informed by Sidani and Irvine's (1999) conceptual framework for evaluating the nurse practitioner role in acute care settings. The synthesis included 43 research articles, which were retrieved following a search of the Cumulative Index to Nursing and Allied Health Literature (CINAHL) bibliographic database. Approximately 60% of the articles were descriptive or qualitative studies, whereas only 7% were randomized controlled trials. Findings suggest that although many outcomes of care have been evaluated, no outcomes have been evaluated consistently and many are not specific to the intervention or actions of nurse practitioners. In addition, few research articles provide information on the educational preparation and experience of the ENPs or the parameters of their practice. Such information is needed to explain the variability observed in the outcomes achieved and to build a body of evidence supporting the role of nurse practitioners in the emergency department.
Multicenter assessment of the rapid Unyvero Blood Culture molecular assay
Authors: Burrack-Lange Sandra Christina , Personne Yoann , Huber Monika , Winkler Elisabeth , Weile Jan , Knabbe Cornelius , Görig Julia , Rohde Holger
Published: July 2018

Purpose. Bloodstream infections remain an important cause of morbidity and mortality. Rapid diagnosis can reduce the time from empiric antimicrobial therapy to targeted therapy and improve patient outcomes.

Methodology. The fully automated Unyvero Blood Culture (BCU) Application (Curetis GmbH) can identify a broad panel of pathogens (36 analytes covering over 50 pathogens) and 16 antibiotic resistance gene markers simultaneously in about 5 h. The assay was evaluated in three clinical laboratories in comparison to routine microbiological procedures.

Results. A total of 207 blood cultures were included in the study, and 90.5 % of the species identified by culture were covered by the Unyvero BCU panel with an overall sensitivity of 96.8 % and specificity of 99.8 %. The time to result was reduced on average by about 34 h. The assay accurately identified 95 % of the species, including 158/164 monomicrobial and 7/9 polymicrobial cultures. The Unyvero BCU Cartridge detected a large number of resistance markers including mecA (n=57), aac(6′)aph(2′′) (n=40), one vanB resistance gene, and six instances of bla
CTX-M.

Conclusion. The Unyvero BCU Application provided fast, reliable results, while significantly improving turnaround time in blood culture diagnostics.
MOB-suite: software tools for clustering, reconstruction and typing of plasmids from draft assemblies
Authors: Robertson James , Nash John H. E.
Published: July 2018

Large-scale bacterial population genetics studies are now routine due to cost-effective Illumina short-read sequencing. However, analysing plasmid content remains difficult due to incomplete assembly of plasmids. Bacterial isolates can contain any number of plasmids and assembly remains complicated due to the presence of repetitive elements. Numerous tools have been developed to analyse plasmids but the performance and functionality of the tools are variable. The MOB-suite was developed as a set of modular tools for reconstruction and typing of plasmids from draft assembly data to facilitate characterization of plasmids. Using a set of closed genomes with publicly available Illumina data, the MOB-suite identified contigs of plasmid origin with both high sensitivity and specificity (95 and 88 %, respectively). In comparison, plasmidfinder demonstrated high specificity (99 %) but limited sensitivity (50 %). Using the same dataset of 377 known plasmids, MOB-recon accurately reconstructed 207 plasmids so that they were assigned to a single grouping without other plasmid or chromosomal sequences, whereas plasmidSPAdes was only able to accurately reconstruct 102 plasmids. In general, plasmidSPAdes has a tendency to merge different plasmids together, with 208 plasmids undergoing merge events. The MOB-suite reduces the number of errors but produces more hybrid plasmids, with 84 plasmids undergoing both splits and merges. The MOB-suite also provides replicon typing similar to plasmidfinder but with the inclusion of relaxase typing and prediction of conjugation potential. The MOB-suite is written in Python 3 and is available from https://github.com/phac-nml/mob-suite.
Exploration of Plant Biodiversity to Investigate Regulation of Photosynthesis in Natural Environment
Authors: Sello Simone , Alboresi Alessandro , Baldan Barbara , Morosinotto Tomas
Published: July 2018

Photosynthesis is regulated in response to dynamic environmental conditions to satisfy plant metabolic demand but also to avoid over-excitation of the electron transport chain generating harmful reactive oxygen species. Photosynthetic organisms evolved several mechanisms to modulate light harvesting and electron transport efficiency to respond to conditions changing at different timescales, going from fast sun flecks to slow seasonal variations.

These regulatory mechanisms changed during evolution of photosynthetic organisms, also adapting to various ecological niches. The investigation of plant biodiversity is valuable to uncover conserved traits and plasticity of photosynthetic regulation. In this work a set of plants belonging to different genera of angiosperms, gymnosperms, ferns and lycophytes was investigated by monitoring their photosynthetic parameters in different seasons, looking for common trends and differences. In all plants analysed photosynthetic electron transport rate was found to be modulated by growth light intensity, ensuring a balance between available energy and photochemical capacity. Growth light also influenced the threshold where heat dissipation of excitation energy, also called Non-Photochemical Quenching (NPQ), was activated. On the contrary NPQ amplitude did not correlate with light intensity experienced by the plants but was a species-specific feature.

NPQ zeaxanthin-dependent component, qZ, was found to be the most variable between different plants, modulating the intensity of the response but also the kinetic properties of its activation and relaxation. The slower NPQ component, qI, was instead found to be uncorrelated with photoinhibition eventually suffered by plants.
Meiotic Double-Strand Break Proteins Influence Repair Pathway Utilization
Authors: Yanowitz Judith L. , Macaisne Nicolas , Kessler Zebulin
Published: July 2018

Double-strand breaks (DSBs) are among the most deleterious lesions DNA can endure. Yet, DSBs are programmed at the onset of meiosis and are required to facilitate appropriate reduction of ploidy in daughter cells. Repair of these break is tightly controlled to favor homologous recombination (HR), the only repair pathway that can form crossovers. However, little is known about how the activities of alternative repair pathways are regulated at these stages. We discovered an unexpected synthetic interaction between the DSB machinery and strand-exchange proteins. Depleting theC. elegansDSB-promoting factors HIM-5 and DSB-2 suppresses the formation of chromosome fusions that arise in the absence of RAD-51 or other strand-exchange mediators. Our investigations reveal that non-homologous and theta-mediated end joining (c-NHEJ and TMEJ, respectively) and single strand annealing (SSA) function redundantly to repair DSBs when HR is compromised and that HIM-5 influences the utilization of TMEJ and SSA.
Microbial composition of enigmatic bird parasites:WolbachiaandSpiroplasmaare the most important bacterial associates of quill mites (Acari: Syringophilidae)
Authors: Glowska Eliza , Filutowska Zuzanna K. , Dabert Miroslawa , Gerth Michael
Published: July 2018

The microbiome is an integral component of many animal species, potentially affecting behaviour, physiology, and other biological properties. Despite this importance, bacterial communities remain vastly understudied in many groups of invertebrates, including mites. Quill mites (Acariformes: Syringophilidae) are a poorly known group of permanent bird ectoparasites that occupy quills of feathers and feed on bird subcutaneous tissue and fluids. Most species have strongly female biased sex ratios and it was hypothesized that this is caused by endosymbiotic bacteria. Their peculiar lifestyle further makes them potential vectors for bird diseases. Previously,Anaplasma phagocytophilumand a high diversity ofWolbachiastrains were detected in quill mites via targeted PCR screens. Here, we use an unbiased 16S amplicon sequencing approach to determine other Bacteria that potentially impact quill mite biology.

We performed 16S V4 amplicon sequencing of 126 quill mite individuals from eleven species parasitizing twelve bird species (four families) of passeriform birds. In addition toWolbachia, we foundSpiroplasmaas potential symbiont of quill mites. Interestingly, consistently highSpiroplasmatitres were only found in individuals of two mite species associated with finches of the genusCardfuelis, suggesting a history of horizontal transfers ofSpiroplasmavia the bird host. Furthermore, there was evidence forSpiroplasmanegatively affectingWolbachiatitres. We found no evidence for the previously reportedAnaplasmain quill mites, but detected the potential pathogensBrucellaandBartonellaat low abundances. Other amplicon sequence variants (ASVs) could be assigned to a diverse number of bacterial taxa, including several that were previously isolated from bird skin. We observed a relatively uniform distribution of these ASVs across mite taxa and bird hosts, i.e, there was a lack of host-specificity for most detected ASVs. Further, many frequently found ASVs were assigned to taxa that show a very broad distribution with no strong prior evidence for symbiotic association with animals. We interpret these findings as evidence for a scarcity or lack of resident microbial associates (other than inherited symbionts) in quill mites, or for abundances of these taxa below our detection threshold.
Social information impairs reward learning in depressive subjects: behavioral and computational characterization
Authors: Safra Lou , Chevallier Coralie , Palminteri Stefano
Published: July 2018

Depression is characterized by a marked decrease in social interactions and blunted sensitivity to rewards. Surprisingly, despite the importance of social deficits in depression, non-social aspects have been disproportionally investigated. As a consequence, the cognitive mechanisms underlying atypical decision-making in social contexts in depression are poorly understood. In the present study, we investigate whether deficits in reward processing interact with the social context and how this interaction is affected by self-reported depression and anxiety symptoms. Two cohorts of subjects (discovery and replication sample:N= 50 each) took part in a task involving reward learning in a social context with different levels of social information (absent, partial and complete). Behavioral analyses revealed a specific detrimental effect of depressive symptoms – but not anxiety – on behavioral performance in the presence of social information, i.e. when participants were informed about the choices of another player. Model-based analyses further characterized the computational nature of this deficit as a negative audience effect, rather than a deficit in the way others’ choices and rewards are integrated in decision making. To conclude, our results shed light on the cognitive and computational mechanisms underlying the interaction between social cognition, reward learning and decision-making in depressive disorders.
A computational observer model of spatial contrast sensitivity: Effects of wavefront-based optics, cone mosaic structure, and inference engine
Authors: Cottaris Nicolas P. , Jiang Haomiao , Ding Xiaomao , Wandell Brian A. , Brainard David H.
Published: July 2018

We present a computational observer model of the human spatial contrast sensitivity (CSF) function based on the Image Systems EngineeringTools for Biology (ISETBio) simulation framework. We demonstrate that ISETBio-derived CSFs agree well with CSFs derived using traditional ideal observer approaches, when the mosaic, optics, and inference engine are matched. Further simulations extend earlier work by considering more realistic cone mosaics, more recent measurements of human physiological optics, and the effect of varying the inference engine used to link visual representations to psy-chohysical performance. Relative to earlier calculations, our simulations show that the spatial structure of realistic cone mosaics reduces upper bounds on performance at low spatial frequencies, whereas realistic optics derived from modern wavefront measurements lead to increased upper bounds high spatial frequencies. Finally, we demonstrate that the type of inference engine used has a substantial effect on the absolute level of predicted performance. Indeed, the performance gap between an ideal observer with exact knowledge of the relevant signals and human observers is greatly reduced when the inference engine has to learn aspects of the visual task. ISETBio-derived estimates of stimulus representations at different stages along the visual pathway provide a powerful tool for computing the limits of human performance.
Overlap graph-based generation of haplotigs for diploids and polyploids
Authors: Baaijens Jasmijn A. , Schönhuth Alexander
Published: July 2018

Haplotype aware genome assembly plays an important role in genetics, medicine, and various other disciplines, yet generation of haplotype-resolved de novo assemblies remains a major challenge. Beyond distinguishing between errors and true sequential variants, one needs to assign the true variants to the different genome copies. Recent work has pointed out that the enormous quantities of traditional NGS read data have been greatly underexploited in terms of haplotig computation so far, which reflects that methodology for reference independent haplotig computation has not yet reached maturity. We present POLYTE (POLYploid genome fitTEr) as a new approach to de novo generation of haplotigs for diploid and polyploid genomes. Our method follows an iterative scheme where in each iteration reads or contigs are joined, based on their interplay in terms of an underlying haplotype-aware overlap graph. Along the iterations, contigs grow while preserving their haplotype identity. Benchmarking experiments on both real and simulated data demonstrate that POLYTE establishes new standards in terms of error-free reconstruction of haplotype-specific sequence. As a consequence, POLYTE outperforms state-of-the-art approaches in various relevant aspects, where advantages become particularly distinct in polyploid settings. POLYTE is freely available as part of the HaploConduct package at https://github.com/HaploConduct/HaploConduct, implemented in Python and C++.
Radial Glia cell infection byToxoplasma gondiidisrupts brain microvascular endothelial cell integrity
Authors: Adesse Daniel , Marcos Anne Caroline , Siqueira Michele , Cascabulho Cynthia M. , Waghabi Mariana C. , Barbosa Helene S. , Stipursky Joice
Published: July 2018

Congenital toxoplasmosis is a parasitic disease that occurs due vertical transmission of the protozoanToxoplasma gondii(T. gondii) during pregnancy. The parasite crosses the placental barrier and reaches the developing brain, infecting progenitor, glial, neuronal and vascular cell types. Although the role of Radial glia (RG) neural stem cells in the development of the brain vasculature has been recently investigated, the impact ofT. gondiiinfection in these events is not yet understood. Herein, we studied the role ofT. gondiiinfection on RG cell function and its interaction with endothelial cells. By infecting isolated RG cells withT. gondiitachyzoites, we observed reduced cell proliferation and neurogenesis without affecting gliogenesis levels. Conditioned medium (CM) from RG control cultures increased ZO-1 and β-catenin protein levels and organization on endothelial bEnd.3 cells membranes, which was completely impaired by CM from infected RG, resulting in decreased transendothelial electrical resistance (TEER). Cytokine Bead Array and ELISA assays revealed the presence of increased levels of the pro-inflammatory cytokine IL-6 and reduced levels of anti-inflammatory cytokine TGF-β1 in CM fromT.gondii-infected RG cells. Treatment with recombinant TGF-β1 concomitantly with CM from infected RG cultures led to restoration of ZO-1 staining in bEnd.3 cells. Our results suggest that infection of RG cells byT. gondiimodulate cytokine secretion, which might contribute to endothelial loss of barrier properties, thus leading to impairment of neurovascular interaction establishment.
Local adaptation of a dominant coastal tree to freshwater availability and solar radiation suggested by genomic and ecophysiological approaches
Authors: Cruz Mariana Vargas , Mori Gustavo Maruyama , Müller Caroline Signori , da Silva Carla Cristina , Oh Dong-Ha , Dassanayake Maheshi , Zucchi Maria Imaculada , Oliveira Rafael Silva , de Souza Anete Pereira
Published: July 2018

Local adaptation is often a product of environmental variations in the geographical space and has implications for biodiversity conservation. We investigated the role of latitudinal heterogeneity in climate on the organization of genetic and phenotypic variation in the dominant coastal tree,Avicennia schaueriana. In a common garden experiment, samples from an equatorial region, marked by rainy/dry seasons, accumulated less biomass, showed lower stomatal conductance and transpiration, narrower xylem vessels, smaller leaves and higher reflectance of long wavelengths (red light) on the stem epidermis, than samples from a subtropical region, marked by warm/cold seasons. Transcriptome differences identified between trees sampled under field conditions at equatorial and subtropical sites, were enriched in functional categories as responses to temperature, solar radiation, water deficit, photosynthesis and cell wall biosynthesis. The diversity based on thousands of SNP loci revealed a north-south genetic structure. Remarkably, signatures of selection were identified in loci associated with photosynthesis, anthocyanin accumulation and the responses to osmotic and hypoxia stresses. Our results suggest the existence of divergence in key resource-use characteristics, likely driven by climate seasonality, based on water-deficit and solar radiation. These findings provide a basis for conservation plans and for predictions for coastal plant responses to climate change.
Infectious bursal disease virus suppresses H9N2 avian influenza viral shedding in broiler chickens
Authors: Ranjbar Vahid Reza , Mohammadi Ali , Dadras Habibollah , Bidadkosh Arash
Published: July 2018

Infectious bursal disease (Gumboro) virus causes immunosuppression in chickens, increasing their susceptibility to other viral and bacterial diseases and resulting in vaccination failure. In the present study, we investigated the immune-depressing effect of infectious bursal disease virus on H9N2 avian influenza viral infection in commercial broiler chickens. Chickens were divided into four groups. In group A, chickens were inoculated with Gumboro virus at 21 days of age and H9N2 influenza virus 5 days later. Groups B and C only received influenza virus at 26 days of age and Gumboro virus at 21 days, respectively. Chickens in the control group (D) were inoculated with normal saline at the same times.

Tissue samples from different organs were collected on days 1, 3, 6, 9, and 12 after H9N2 infection. Macroscopic observation showed bursal disease lesions in groups A and C, including swollen bursa with the presence of gelatinous exudates, hemorrhages in the thigh muscle, edema, and nephritis.

Reverse transcription polymerase chain reaction was used to study H9N2 influenza virus dissemination, and quantitative reverse transcription polymerase chain reaction to determine viral genome copy number in different organs. A considerable titer of avian influenza virus was found in the trachea, lungs, cecal tonsils, spleens, and feces of infected chickens. The genome copy number of the virus in the trachea and lungs of group A was significantly higher than that in group B on the first day after inoculation. However, our method did not detect the avian influenza virus genome in group A. In conclusion, we suggest that pre-exposure to Gumboro virus at 3 weeks of age reduces the replication and shedding of H9N2 in broiler chicken.
The permeabilized SecY protein-translocation channel can serve as a nonspecific sugar transporter
Authors: Mei Sen , Xie Chong , Mi Hao , Xue Chuang , Guo Qiang , Du Guang-Qing , Li Guo-Bei , Li Cai-Xia , Qu Ya-Nan , Xiong Ming-Hao , Jiang Yang , Tan Tian-Wei , Yang Shang-Tian , Fan Li-Hai
Published: July 2018

As the initial step in carbohydrate catabolism in cells, the substrate-specific transporters via active transport and facilitated diffusion play a decisive role in passage of sugars through the plasma membrane into the cytoplasm. The SecY complex (SecYEG) in bacteria forms a membrane channel responsible for protein translocation. This work demonstrates that weakening the sealability of the SecY channel allowed free diffusion of sugars, including glucose, fructose, mannose, xylose, arabinose, and lactose, into the engineered cells, facilitating its rapid growth on a wide spectrum of monosaccharides and bypassing/reducing stereospecificity, transport saturation, competitive inhibition, and carbon catabolite repression (CCR), which are usually encountered with the specific sugar transporters. The SecY channel is structurally conserved in prokaryotes, thus it may be engineered to serve as a unique and universal transporter for bacteria to passage sugars as demonstrated inEscherichia coliandClostridium acetobutylicum.
Computer simulation of knotted proteins unfold and translocation through nano-pores
Authors: Shahzad M. A.
Published: July 2018

We study the unfold and translocation of knotted protein, YibK and YbeA, through α-hemolysin nano-pore via a coarse grained computational model. We observe that knot of protein unfold in advance before the translocation take place. We also characterized the translocation mechanism by studying the thermodynamical and kinetic properties of the process. In particular, we study the average of translocation time, and the translocation probability as a function of pulling force F acting in the channel. In limit of low pulling inward constant force acting along the axis of the pore, the YibK knotted protein takes longer average translocation time as compare to YbeA knotted protein.
A novel enhancer RNA, Hmrhl, positively regulates its host gene,phkb,in Chronic Myelogenous Leukemia
Authors: Fatima Roshan , Choudhury Subhendu Roy , Divya T. R. , Bhaduri Utsa , Rao M. R. S.
Published: July 2018

Noncoding RNAs are increasingly being accredited with key roles in gene regulation during development and disease. Here we report the discovery and characterization of a novel long noncoding RNA, Hmrhl, which shares synteny and partial sequence similarity with the mouse lncRNA, Mrhl. The human homolog, Hmrhl, transcribed from intron 14 ofphkbgene, is 5.5kb in size, expressed in all tissues examined and has acquired additional repeat elements. Analysis of Hmrhl locus using ENCODE database revealed that it is associated with hallmarks of enhancers like the open chromatin configuration, binding of transcription factors, enhancer specific histone signature etc. in the K562 Chronic Myelogenous Leukemia (CML) cells. We compared the expression of Hmrhl in the normal lymphoblast cell line, GM12878, with that of K562 cells and lymphoma samples and show that it is highly upregulated in leukemia as well as several cases of lymphoma. We validated the enhancer properties of Hmrhl locus in K562 cells with the help of Luciferase assay. Moreover, siRNA mediated down-regulation of Hmrhl in K562 cells leads to a concomitant down regulation of its parent gene,phkb, showing that Hmrhl functions as an enhancer RNA and positively regulates its host gene,phkb,in chronic myelogenous leukemia.
A Cytoplasmic GOLD Protein Controls Cell Polarity
Authors: Omnus Deike J. , Cadou Angela , Chung Gary H.C. , Bader Jakob M. , Stefan Christopher J.
Published: July 2018

Phosphoinositide lipids provide spatial landmarks during polarized secretion. Here, we elucidate a role for phosphatidylinositol 4-phosphate (PI4P) metabolism in the control of cell polarity. In budding yeast, PI4P is enriched at the plasma membrane of growing daughter cells. Upon heat shock however, PI4P rapidly increases at the plasma membrane in mother cells resulting in a more uniform PI4P distribution. Rather than phosphoinositide kinase activation, PI4P hydrolysis is impaired to generate the heat-induced PI4P signal in mother cells. This fine tune control of PI4P metabolism is mediated through attenuation of the Osh3 protein that binds and presents PI4P to a phosphoinositide phosphatase. Importantly, Osh3 undergoes phase transitions upon environmental stress conditions, resulting in intracellular aggregates and reduced cortical localization. The chaperone Hsp104 co-assembles with intracellular Osh3 granules, but is not required for their formation. Interestingly, the Osh3 GOLD domain, also present in the ER-localized p24 cargo adaptor family, is sufficient to form stress granules. Accordingly, GOLD-mediated phase transitions may provide a general mechanism to modulate secretion and growth upon transient changes in physiological and environmental conditions.
Neurons of the inferior olive respond to broad classes of sensory input while subject to homeostatic control
Authors: Ju Chiheng , Bosman Laurens W.J. , Hoogland Tycho M. , Velauthapillai Arthiha , Murugesan Pavithra , Warnaar Pascal , van Genderen Romano M. , Negrello Mario , De Zeeuw Chris I.
Published: July 2018

Cerebellar Purkinje cells integrate sensory information with motor efference copies to adapt movements to behavioural and environmental requirements. They produce complex spikes that are triggered by the activity of climbing fibres originating in neurons of the inferior olive. These complex spikes can shape the onset, amplitude and direction of movements as well as the adaptation of such movements to sensory feedback. Clusters of nearby inferior olive neurons project to parasagittally aligned stripes of Purkinje cells, referred to as “microzones”. It is currently unclear to what extent individual Purkinje cells within a single microzone integrate climbing fibre inputs from multiple sources of different sensory origins, and to what extent sensory-evoked climbing fibre responses depend on the strength and recent history of activation. Here we imaged complex spike responses in cerebellar lobule crus 1 to various types of sensory stimulation in awake mice. We find that different sensory modalities and receptive fields have a mild, but consistent, tendency to converge on individual Purkinje cells. Purkinje cells encoding the same stimulus show increased events with coherent complex spike firing and tend to lie close together. Moreover, whereas complex spike firing is only mildly affected by variations in stimulus strength, it strongly depends on the recent history of climbing fibre activity. Our data point towards a mechanism in the olivo-cerebellar system that regulates complex spike firing during mono- or multisensory stimulation around a relatively low set-point, highlighting an integrative coding scheme of complex spike firing under homeostatic control.
Probing the Modularity of Megasynthases by Rational Engineering of a Fatty Acid Synthase (FAS) Type I
Authors: Rittner Alexander , Paithankar Karthik S. , Drexler David , Himmler Aaron , Grininger Martin
Published: July 2018

Modularity is an aspect of a decomposable system with a coordinating authority that acts as a glue which holds the loosely held components. These multi-component entities (“modules”) facilitate rewiring into different designs allowing for change. Such modular character is a fundamental property of many biological entities, especially the family of megasynthases such as polyketide synthases (PKSs). The ability of these PKSs to produce diverse product spectra is strongly coupled to their broad architectural modularity. Decoding the molecular basis of modularity, i.e. identifying the folds and domains that comprise the modules as well as understanding constrains of the assembly of modules, is of utmost importance for harnessing megasynthases for the synthesis of designer compounds. In this study, we exploit the close semblance between PKSs and animal FAS to re-engineer animal FAS to probe the modularity of the FAS/PKS family. Guided by structural and sequence information, we truncate and dissect animal FAS into its components, and reassemble them to generate new PKS-like modules as well as bimodular constructs. The novel engineered modules resemble all four common module types of PKSs and demonstrate that this approach can be a powerful tool to create higher catalytic efficiency. Our data exemplify the inherent plasticity and robustness of the overall FAS/PKS fold, and open new avenues to explore FAS-based biosynthetic pathways for custom compound design.
Signal propagation in metal-rich railway environment
Authors: Nikolic Bojana , Dimitrijevic Bojan , Hutschenreuther Tino , Toepfer Hannes
Published: July 2018

Purpose

The purpose of this paper is to analyze a signal propagation in highly metalized environments, which has not been extensively studied in the literature. Having in mind a large number of such applications, better understanding and possibly finding a way of improving communication in these conditions would be highly beneficial.

Design/methodology/approach

The analysis is performed in a simulation environment developed by the authors, based on finite difference time domain (FDTD) method, to identify effects that have decisive influence on electromagnetic (EM) wave propagation in the aforementioned conditions. The analysis of the EM field at the reception is modified so that a multiple-field sampling is performed, and maximal values are further used. In practical realizations, this procedure could be implemented by using multiple antennas and selective combining at the reception.

Findings

Results show that the existence of metal objects (in the observed case, these are railway tracks), in combination with the appropriate choice of antenna parameters, can be favorably used to improve signal reception. The contribution is manifested through the reduction of the pathloss.

Research limitations/implications

In the performed analysis, one should be aware of the limitations that the FDTD method brings. Those limitations are related to the size of the computational domain and discretization mesh refinement (possibility of modeling geometry in fine details).

Originality/value

Originality of this paper consists of the introduced modification in the analysis of signal propagation in heavily metalized environment. Namely, a multiple-field sampling in the reception zone (in one plane, dimensions λ × λ = 12.5 cm X 12.5 cm) is performed using several probes in simulation environment. In this way, a qualitative analysis is performed more efficiently, which made it is possible to distinguish and identify different propagation mechanisms.