bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Rotavirus NSP4 Viroporin Domain is a Calcium-conducting Ion Channel
Authors: Pham Thieng , Perry Jacob L. , Dosey Timothy L. , Delcour Anne H. , Hyser Joseph M. 
Published: March 2017

AbstractViroporins are small virus-encoded ion channel proteins. Most viroporins are monovalent selective cation channels, with few showing the ability to conduct divalent cations, like calcium (Ca2+). Nevertheless, some viroporins are known to disrupt host cell Ca2+ homeostasis, which is critical for virus replication and pathogenesis. Rotavirus nonstructural protein 4 (NSP4) is an endoplasmic reticulum transmembrane glycoprotein that has a viroporin domain (VPD), and NSP4 viroporin activity elevates cytosolic Ca2+ in mammalian cells. The goal of this study was to demonstrate that the NSP4 VPD forms an ion channel and determine whether the channel can conduct Ca2+. Using planar lipid bilayer and liposome patch clamp electrophysiology, we show that a synthetic peptide of the NSP4 VPD has ion channel activity. The NSP4 VPD was selective for cations over anions and channel activity was observed to have both well-defined “square top” openings as well as fast current fluctuations, similar to other viroporins. Importantly, the NSP4 VPD showed similar conductance of divalent cations (Ca2+ and Ba2+) as monovalent cations (K+), but a viroporin defective mutant lacked Ca2+ conductivity. These data demonstrate that the NSP4 VPD is a Ca2+-conducting viroporin and establish the mechanism by which NSP4 disturbs host cell Ca2+ homeostasis.
The Beaver’s Phylogenetic Lineage Illuminated by Retroposon Reads
Authors: Doronina Liliya , Matzke Andreas , Churakov Gennady , Stoll Monika , Huge Andreas , Schmitz Jürgen 
Published: March 2017

AbstractSolving problematic phylogenetic relationships often requires high quality genome data. However, for many organisms such data are still not available. Among rodents, the phylogenetic position of the beaver has always attracted special interest. The arrangement of the beaver’s masseter (jaw-closer) muscle once suggested a strong affinity to some sciurid rodents (e.g., squirrels), placing them in the Sciuromorpha suborder. Modern molecular data, however, suggested a closer relationship of beaver to the representatives of the mouse-related clade, but significant data from virtually homoplasy-free markers (for example retroposon insertions) for the exact position of the beaver have not been available. We derived a gross genome assembly from deposited genomic Illumina paired-end reads and extracted thousands of potential phylogenetically informative retroposon markers using the new bioinformatics coordinate extractor fastCOEX, enabling us to evaluate different hypotheses for the phylogenetic position of the beaver. Comparative results provided significant support for a clear relationship between beavers (Castoridae) and kangaroo rat-related species (Geomyoidea) (p < 0.0015, six markers, no conflicting data) within a significantly supported mouse-related clade (including Myodonta, Anomaluromorpha, and Castorimorpha) (p < 0.0015, six markers, no conflicting data).
Cholesterol impairment contributes to neuroserpin aggregation
Authors: Giampietro Costanza , Lionetti Maria Chiara , Costantini Giulio , Mutti Federico , Zapperi Stefano , La Porta Caterina A. M. 
Published: March 2017

AbstractIntraneural accumulation of misfolded proteins is a common feature of several neurodegenerative pathologies including Alzheimer’s and Parkinson’s diseases, and Familial Encephalopathy with Neuroserpin Inclusion Bodies (FENIB). FENIB is a rare disease due to a point mutation in neuroserpin which accelerates protein aggregation in the endoplasmic reticulum (ER). Here we show that cholesterol depletion induced either by prolonged exposure to statins or by inhibiting the sterol reg-ulatory binding-element protein (SREBP) pathway also enhances aggregation of neuroserpin proteins. These findings can be explained considering a computational model of protein aggregation under non-equilibrium conditions, where a decrease in the rate of protein clearance improves aggregation. Decreasing cholesterol in cell membranes affects their biophysical properties, including their ability to form the vesicles needed for protein clearance, as we illustrate by a simple mathematical model. Taken together, these results suggest that cholesterol reduction induces neuroserpin aggregation, even in absence of specific neuroserpin mutations. The new mechanism we uncover could be relevant also for other neurodegenerative diseases associated with protein aggregation.
Real-time observation of the isothermal crystallization kinetics in a deeply supercooled liquid
Authors: Zanatta M. , Cormier L. , Hennet L. , Petrillo C. , Sacchetti F. 
Published: March 2017

AbstractBelow the melting temperature Tm, crystals are the stable phase of typical elemental or molecular systems. However, cooling down a liquid below Tm, crystallization is anything but inevitable. The liquid can be supercooled, eventually forming a glass below the glass transition temperature Tg. Despite their long lifetimes and the presence of strong barriers that produces an apparent stability, supercooled liquids and glasses remain intrinsically a metastable state and thermodynamically unstable towards the crystal. Here we investigated the isothermal crystallization kinetics of the prototypical strong glassformer GeO2 in the deep supercooled liquid at 1100 K, about half-way between Tm and Tg. The crystallization process has been observed through time-resolved neutron diffraction for about three days. Data show a continuous reorganization of the amorphous structure towards the alpha-quartz phase with the final material composed by crystalline domains plunged into a low-density, residual amorphous matrix. A quantitative analysis of the diffraction patterns allows determining the time evolution of the relative fractions of crystal and amorphous, that was interpreted through an empirical model for the crystallization kinetics. This approach provides a very good description of the experimental data and identifies a predator-prey-like mechanism between crystal and amorphous, where the density variation acts as a blocking barrier.
Dose- and time- effect responses of DNA methylation and histone H3K9 acetylation changes induced by traffic-related air pollution
Authors: Ding Rui , Jin Yongtang , Liu Xinneng , Ye Huaizhuang , Zhu Ziyi , Zhang Yuan , Wang Ting , Xu Yinchun 
Published: March 2017

AbstractAs an important risk factor of respiratory disorders, traffic-related air pollution (TRAP) has caused extensive concerns. Epigenetic change has been considered a link between TRAP and respiratory diseases. However, the exact effects of TRAP on epigenetic changes are still unclear. Here we investigated the dose- and time- effect responses of TRAP on DNA methylations and H3K9 acetylation (H3K9ac) in both blood and lung tissues of rats. The findings showed that every 1 μg/m3 increase of TRAP components were associated with changes in %5 mC (95% CI) in LINE-1, iNOS, p16CDKN2A, and APC ranging from −0.088% (−0.150, −0.026) to 0.102 (0.049, 0.154), as well as 0.276 (0.053, 0.498) to 0.475 (0.103, 0.848) ng/mg increase of H3K9ac. In addition, every 1 more day exposure at high level of TRAP (in tunnel) also significantly changed the levels of DNA methylation (ranging from −0.842% to 0.248%) and H3K9ac (16.033 and 15.718 ng/mg pro in PBMC and lung tissue, respectively) changes. Season and/or sex could interact with air pollutants in affecting DNA methylation and H3K9ac. The findings showed that TRAP exposure is dose- and time- dependently associated with the changes of DNA methylation and H3K9ac.
Chemosensory adaptations of the mountain fly Drosophila nigrosparsa (Insecta: Diptera) through genomics’ and structural biology’s lenses
Authors: Cicconardi Francesco , Di Marino Daniele , Olimpieri Pier Paolo , Arthofer Wolfgang , Schlick-Steiner Birgit C. , Steiner Florian M. 
Published: March 2017

AbstractChemoreception is essential for survival. Some chemicals signal the presence of nutrients or toxins, others the proximity of mating partners, competitors, or predators. Chemical signal transduction has therefore been studied in multiple organisms. InDrosophilaspecies, a number of odorant receptor genes and various other types of chemoreceptors were found. Three main gene families encode for membrane receptors and one for globular proteins that shuttle compounds with different degrees of affinity and specificity towards receptors. By sequencing the genome ofDrosophila nigrosparsa, a habitat specialist restricted to montane/alpine environment, and combining genomics and structural biology techniques, we characterised odorant, gustatory, ionotropic receptors and odorant binding proteins, annotating 189 loci and modelling the protein structure of two ionotropic receptors and one odorant binding protein. We hypothesise that theD. nigrosparsagenome experienced gene loss and various evolutionary pressures (diversifying positive selection, relaxation, and pseudogenisation), as well as structural modification in the geometry and electrostatic potential of the two ionotropic receptor binding sites. We discuss possible trajectories in chemosensory adaptation processes, possibly enhancing compound affinity and mediating the evolution of more specialized food, and a fine-tuned mechanism of adaptation.
Spore surface proteins of Brevibacillus laterosporus are involved in insect pathogenesis
Authors: Marche Maria Giovanna , Mura Maria Elena , Falchi Giovanni , Ruiu Luca 
Published: March 2017

AbstractOuter spore envelope proteins of pathogenic bacteria often present specific virulence factors and tools to evade the defence system of their hosts. Brevibacillus laterosporus, a pathogen of invertebrates and an antimicrobial-producing species, is characterised by a unique spore coat and canoe-shaped parasporal body (SC-CSPB) complex surrounding the core spore. In the present study, we identified and characterised major proteins of the SC-CSPB complex of B. laterosporus, and we investigated their entomopathogenic role. Employing a proteomic approach and a B. laterosporus-house fly study model, we found four highly conserved proteins (ExsC, CHRD, CpbA and CpbB) that function as insect virulence factors. CpbA was associated with a significantly higher mortality of flies and greater relative gene expression levels during sporulation, compared to the other SC-CSPB proteins. Taken together, we suggest that spore surface proteins are a part of a complex set of toxins and virulence factors that B. laterosporus employs in its pathogenicity against flies.
Guideline Compliance in Surgery for Thyroid Nodules – A Retrospective Study
Authors: Reinisch A. , Malkomes P. , Habbe N. , Bojunga J. , Grünwald F. , Badenhoop K. , Bechstein W. , Holzer K. 
Published: March 2017

Abstract
Diagnostic guidelines for thyroid nodules focus on malignancy risk assessment to avoid unnecessary diagnostic operations. These guidelines recommend a combination of tests in form of a diagnostic algorithm. The present study analyzed the recommended algorithm and its implementation by different medical professionals.
Preoperative diagnostic procedures, laboratory tests and histopathological findings of patients who underwent thyroid surgery between 2006 and 2013 were analyzed. The results were stratified by the assignation by specialized endocrinologists (ENP), general practitioners (GP) or Goethe-University Hospital Frankfurt (UKF).
677 patients were enrolled, of these 62% were assigned by UKF, 18.5% by an ENP and 19.5% by a GP. Ultrasonography rate was significantly higher in UKF (97.6%) compared to patients assigned by GP (90.9%, p<0.0001). Rates for fine-needle aspiration cytology ranged between 47.6% in UKF and 23.2% in ENP (p<0.0001). In over 93% of the patients an analysis of thyroid-stimulating hormone and triiodothyronine/thyroxin was realized. The overall malignancy rate was 11.82%. The malignancy rate was significantly higher if a FNA biopsy was performed (16.35 vs. 8.94%; p=0.0048).
A higher malignancy rate could only be seen if the preoperative diagnostic workup included FNA. Besides this, the grade of algorithm adherence showed no effect on the malignancy rate.
Optogenetik – eine Chance für fortgeschrittene retinale Dystrophien
Authors: Swiersy A. , Klapper S. , Busskamp V. 
Published: March 2017

ZusammenfassungDie Optogenetik nutzt genetisch modifizierte lichtaktive Proteine, um Zellen durch Licht nicht invasiv zu manipulieren. Der Prototyp dieser Proteine ist Channelrhodopsin2 (ChR2), ein unselektiver Kationenkanal. Dieser kann elektrisch erregbare Zellen durch Lichtimpulse depolarisieren. Die Kombination von Channelrhodopsin und Halorhodopsin (eNpHR), eine hyperpolarisierende lichtgetriebene Cl−-Pumpe, ermöglicht eine komplexe Modulation neuronaler Aktivität sowohl in vitro als auch in vivo. Sehr schnell stellte sich heraus, dass die Optogenetik für die Behandlung von Sehbehinderungen, die mit der Degeneration der Photorezeptoren einhergehen, gute Chancen zur Therapie bietet. Dabei werden funktionslose Photorezeptoren durch die ektopische Expression der hyperpolarisierenden Pumpe eNpHR reaktiviert. Aber auch andere Zellen der Retina können durch die induzierte Expression von ChR2 die Aufgabe des Lichtempfangs übernehmen und damit zu künstlichen Photorezeptoren werden. Mit diesem Übersichtsartikel möchten wir eine kurze Einführung zur Retina und deren Rolle sowohl in der physiologischen als auch in der pathologischen Lichtwahrnehmung geben. Weiterhin werden optogenetische Strategien zur Wiederherstellung der Lichtwahrnehmungen aufgezeigt und strukturelle sowie funktionelle Eigenschaften der auf Rhodopsin basierenden optogenetischen Werkzeuge diskutiert. Letztendlich wird die Anwendbarkeit für die Wiederherstellung des Sehvermögens durch die Optogenetik bewertet.
EliIE: An open-source information extraction system for clinical trial eligibility criteria
Authors: Kang Tian , Zhang Shaodian , Tang Youlan , Hruby Gregory W , Rusanov Alexander , Elhadad Noémie , Weng Chunhua 
Published: March 2017

AbstractObjectiveTo develop an open-source information extraction system called Eligibility Criteria Information Extraction (EliIE) for parsing and formalizing free-text clinical research eligibility criteria (EC) following Observational Medical Outcomes Partnership Common Data Model (OMOP CDM) version 5.0.Materials and MethodsEliIE parses EC in 4 steps: (1) clinical entity and attribute recognition, (2) negation detection, (3) relation extraction, and (4) concept normalization and output structuring. Informaticians and domain experts were recruited to design an annotation guideline and generate a training corpus of annotated EC for 230 Alzheimer’s clinical trials, which were represented as queries against the OMOP CDM and included 8008 entities, 3550 attributes, and 3529 relations. A sequence labeling–based method was developed for automatic entity and attribute recognition. Negation detection was supported by NegEx and a set of predefined rules. Relation extraction was achieved by a support vector machine classifier. We further performed terminology-based concept normalization and output structuring.ResultsIn task-specific evaluations, the best F1 score for entity recognition was 0.79, and for relation extraction was 0.89. The accuracy of negation detection was 0.94. The overall accuracy for query formalization was 0.71 in an end-to-end evaluation.ConclusionsThis study presents EliIE, an OMOP CDM–based information extraction system for automatic structuring and formalization of free-text EC. According to our evaluation, machine learning-based EliIE outperforms existing systems and shows promise to improve.
Evolution of Sagittal Imbalance Following Corrective Surgery for Sagittal Plane Deformity
Authors: McDowell Michael M. , Tempel Zachary J. , Gandhoke Gurpreet S. , Khattar Nicholas K. , Hamilton D. Kojo , Kanter Adam S. , Okonkwo David O. 
Published: March 2017

Abstract

BACKGROUND: Sagittal balance in adult spinal deformity is a major predictor of quality of life. A temporary loss of paraspinal muscle force and somatic pain following spine surgery may limit a patient's ability to maintain posture.

OBJECTIVE: To assess the evolution of sagittal balance and clinical outcomes during recovery from adult spinal deformity surgery.

METHODS: Retrospective review of a prospective observational database identified a consecutive series of patients with sagittal vertical axis (SVA) > 40 mm undergoing adult deformity surgery. Radiographic parameters and clinical outcomes were measured out to 2 yr after surgery.

RESULTS: A total of 113 consecutive patients met inclusion criteria. Mean preoperative SVA was 90.3 mm, increased to 104.6 mm in the first week, then gradually reduced at each follow-up interval to 59.2 mm at 6 wk, 45.0 mm at 3 mo, 38.6 mm at 6 mo, and 34.1 mm at 1 yr (all P < .05). SVA did not change between 1 and 2 yr. Pelvic incidence-lumbar lordosis (PI-LL) corrected immediately from 25.3° to 8.5° (16.8° change; P < .01) and a decreased pelvic tilt from 27.6° to 17.6° (10° change; P < .01). No further change was noted in PI-LL. Pelvic tilt increased to 20.2° (P = .01) at 6 wk and held steady through 2 yr. Mean Visual Analog Scale, Oswestry Disability Index, and Short Form-36 scores all improved; pain rapidly improved, whereas disability measures improved as SVA improved.

CONCLUSION: Radiographic assessment of global sagittal alignment did not fully reflect surgical correction of sagittal balance until 6 mo after adult deformity surgery. Sagittal balance initially worsened then steadily improved at each interval over the first year postoperatively. At 1 yr, all clinical and radiographic measures outcomes were significantly improved.
Executive Summary
Authors: Rushton Cynda Hylton , Schoonover-Shoffner Kathy , Kennedy Maureen Shawn 
Published: March 2017

ABSTRACT
To examine practices for addressing moral distress, a collaborative project was developed by the Johns Hopkins Berman Institute of Bioethics, the Johns Hopkins School of Nursing, the American Journal of Nursing, and the Journal of Christian Nursing, along with the American Association of Critical-Care Nurses and the American Nurses Association. Its purpose was to identify strategies that individuals and systems can use to mitigate the detrimental effects of moral distress and foster moral resilience. On August 11 and 12, 2016, an invitational symposium, State of the Science: Transforming Moral Distress into Moral Resilience in Nursing, was held at the Johns Hopkins School of Nursing in Baltimore, Maryland. Forty-five nurse clinicians, researchers, ethicists, organization representatives, and other stakeholders took part. The result of the symposium was group consensus on recommendations for addressing moral distress and building moral resilience in four areas: practice, education, research, and policy. Participants and the organizations represented were energized and committed to moving this agenda forward. The full report is available online at http://journals.lww.com/ajnonline/Pages/Moral-Distress-Supplement.aspx
Customized Corneal Cross-Linking—A Mathematical Model
Authors: Caruso Ciro , Epstein Robert L. , Ostacolo Carmine , Pacente Luigi , Troisi Salvatore , Barbaro Gaetano 
Published: March 2017

Purpose:
To improve the safety, reproducibility, and depth of effect of corneal cross-linking with the ultraviolet A (UV-A) exposure time and fluence customized according to the corneal thickness.

Methods:
Twelve human corneas were used for the experimental protocol. They were soaked using a transepithelial (EPI-ON) technique using riboflavin with the permeation enhancer vitamin E–tocopheryl polyethylene glycol succinate. The corneas were then placed on microscope slides and irradiated at 3 mW/cm2 for 30 minutes. The UV-A output parameters were measured to build a new equation describing the time-dependent loss of endothelial protection induced by riboflavin during cross-linking, as well as a pachymetry-dependent and exposure time-dependent prescription for input UV-A fluence. The proposed equation was used to establish graphs prescribing the maximum UV-A fluence input versus exposure time that always maintains corneal endothelium exposure below toxicity limits.

Results:
Analysis modifying the Lambert–Beer law for riboflavin oxidation leads to graphs of the maximum safe level of UV-A radiation fluence versus the time applied and thickness of the treated cornea. These graphs prescribe UV-A fluence levels below 1.8 mW/cm2 for corneas of thickness 540 μm down to 1.2 mW/cm2 for corneas of thickness 350 μm. Irradiation times are typically below 15 minutes.

Conclusions:
The experimental and mathematical analyses establish the basis for graphs that prescribe maximum safe fluence and UV-A exposure time for corneas of different thicknesses. Because this clinically tested protocol specifies a corneal surface clear of shielding riboflavin on the corneal surface during UV-A irradiation, it allows for shorter UV-A irradiation time and lower fluence than in the Dresden protocol.
Rapid Warming of Donor Corneas Is Safe and Improves Specular Image Quality
Authors: Tran Khoa D. , Clover Jameson , Ansin Amy , Stoeger Christopher G. , Terry Mark A. 
Published: March 2017

Purpose:
To determine whether warming donor corneas to near-physiological temperatures can safely shorten warming times while providing high-quality specular images during tissue evaluation.

Methods:
Mated corneas were warmed at room temperature (RT) or at 35°C for 4 hours upon removal from cold storage. Specular images and endothelial cell densities were acquired and rated every hour. Additional mated corneas were subjected to 2 rounds of 4-hour incubation at either RT or 35°C. Endothelial cell loss (ECL) was quantified 14 days after the initial incubation using Calcein-acetoxymethyl (Calcein-AM) and FIJI trainable segmentation. Cultures inoculated with common ocular pathogens were subjected to 2 warming cycles at RT for 4 hours or 35°C for 2 hours. Colony counts were taken over the course of 2 weeks after inoculation.

Results:
Specular image quality ratings were consistently higher for corneas warmed at 35°C compared with those at RT. Image quality ratings for corneas warmed at 35°C for 1.5 hours were higher than corneas warmed at RT for 4 hours (P = 0.04). No differences in ECL were observed between the 2 warming conditions (RT = 13.1% ± 7.6% ECL, 35°C = 13.9% ± 6% ECL, P = 0.75). There was no difference in colony counts for pathogens tested between the 2 warming conditions.

Conclusions:
Warming donor corneas to near-physiological temperatures for a short time can increase specular image quality while reducing the time tissues are unrefrigerated at eye banks. This method allows for more efficient specular imaging without inducing additional ECL or increasing pathogen growth.