bluuebunny/crossref_metadata_2025 huggingface dataset:
Insight into the molecular mechanism of miR-192 regulating Escherichia coli resistance in piglets
Authors: Sun Li , Wu Sen , Dai Chao-Hui , Sun Shou-Yong , Zhu Guo-Qiang , Wu Sheng-Long , Bao Wen-Bin
Published: January 2018

MicroRNAs (miRNAs) have important roles in many cellular processes, including cell proliferation, growth and development, and disease control. Previous study demonstrated that the expression of two highly homologous miRNAs (miR-192 and miR-215) was up-regulated in weaned piglets with Escherichia coli F18 infection. However, the potential molecular mechanism of miR-192 in regulating E. coli infection remains unclear in pigs. In the present study, we analyzed the relationship between level of miR-192 and degree of E. coli resistance using transcription activator-like effector nuclease (TALEN), in vitro bacterial adhesion assays, and target genes research. A TALEN expression vector that specifically recognizes the pig miR-192 was constructed and then monoclonal epithelial cells defective in miR-192 were established. We found that miR-192 knockout led to enhance the adhesion ability of the E. coli strains F18ab, F18ac and K88ac, meanwhile increase the expression of target genes (DLG5 and ALCAM) by qPCR and Western blotting analysis. The results suggested that miR-192 and its key target genes (DLG5 and ALCAM) could have a key role in E. coli infection. Based on our findings, we propose that further investigation of miR-192 function is likely to lead to insights into the molecular mechanisms of E. coli infection.
RNA helicases in RNA decay
Authors: Khemici Vanessa , Linder Patrick
Published: January 2018

RNA molecules have the tendency to fold into complex structures or to associate with complementary RNAs that exoribonucleases have difficulties processing or degrading. Therefore, degradosomes in bacteria and organelles as well as exosomes in eukaryotes have teamed-up with RNA helicases. Whereas bacterial degradosomes are associated with RNA helicases from the DEAD-box family, the exosomes and mitochondrial degradosome use the help of Ski2-like and Suv3 RNA helicases.
The exon junction complex: structural insights into a faithful companion of mammalian mRNPs
Authors: Gerbracht Jennifer V. , Gehring Niels H.
Published: January 2018

During splicing, the exon junction complex (EJC) is deposited upstream of exon-exon boundaries. The EJC and its peripheral bound proteins play an essential role in mediating mRNA export, translation and turnover. However, the exact sequence of EJC assembly and the involved factors during splicing remain elusive. Recently published structures of the human C* spliceosome clarified the position of the EJC at this phase of splicing and have given insight into previously unidentified interactions between the EJC and spliceosomal proteins. Here, these new observations are presented and the significance for EJC assembly is discussed. Furthermore, the vast landscape of EJC interacting proteins and their manifold functions are described. Finally, the factors involved in EJC disassembly and recycling are recapitulated. This review aims to integrate structural, biochemical and physiological data to obtain a comprehensive picture of EJC components during the lifetime of the EJC.
Intestinal dysbiosis and permeability: the yin and yang in alcohol dependence and alcoholic liver disease
Authors: Stärkel Peter , Leclercq Sophie , de Timary Philippe , Schnabl Bernd
Published: January 2018

Alcohol dependence and alcoholic liver disease represent a major public health problem with substantial morbidity and mortality. By yet incompletely understood mechanisms, chronic alcohol abuse is associated with increased intestinal permeability and alterations of the gut microbiota composition, allowing bacterial components, bacteria, and metabolites to reach the portal and the systemic circulation. These gut-derived bacterial products are recognized by immune cells circulating in the blood or residing in remote organs such as the liver leading to the release of pro-inflammatory cytokines which are considered important mediators of the liver–gut–brain communication. Although circulating cytokines are likely not the sole factors involved, they can induce liver inflammation/damage and reach the central nervous system where they favor neuroinflammation which is associated with change in mood, cognition, and drinking behavior. In this review, the authors focus on the current evidence describing the changes that occur in the intestinal microbiota with chronic alcohol consumption in conjunction with intestinal barrier breakdown and inflammatory changes sustaining the concept of a gut–liver–brain axis in the pathophysiology of alcohol dependence and alcoholic liver disease.
O-Linked β-N-acetylglucosamine (O-GlcNAc) modification: a new pathway to decode pathogenesis of diabetic retinopathy
Authors: Gurel Zafer , Sheibani Nader
Published: January 2018

The incidence of diabetes continues to rise among all ages and ethnic groups worldwide. Diabetic retinopathy (DR) is a complication of diabetes that affects the retinal neurovasculature causing serious vision problems, including blindness. Its pathogenesis and severity is directly linked to the chronic exposure to high glucose conditions. No treatments are currently available to stop the development and progression of DR. To develop new and effective therapeutic approaches, it is critical to better understand how hyperglycemia contributes to the pathogenesis of DR at the cellular and molecular levels. We propose alterations in O-GlcNAc modification of target proteins during diabetes contribute to the development and progression of DR. The O-GlcNAc modification is regulated through hexosamine biosynthetic pathway. We showed this pathway is differentially activated in various retinal vascular cells under high glucose conditions perhaps due to their selective metabolic activity. O-GlcNAc modification can alter protein stability, activity, interactions, and localization. By targeting the same amino acid residues (serine and threonine) as phosphorylation, O-GlcNAc modification can either compete or cooperate with phosphorylation. Here we will summarize the effects of hyperglycemia-induced O-GlcNAc modification on the retinal neurovasculature in a cell-specific manner, providing new insight into the role of O-GlcNAc modification in early loss of retinal pericytes and the pathogenesis of DR.
Energy scaling of the “heartbeat” pulse width of GRS
1915+105, IGR J17091−3624, and MXB 1730−335 from Rossi-XTE observations
Authors: Maselli A. , Capitanio F. , Feroci M. , Massa F. , Massaro E. , Mineo T.
Published: January 2018

We investigate some key aspects of the “heartbeat” variability consisting of series of bursts with a slow rise and a fast decay, thus far detected only in GRS 1915+105, IGR J17091−3624, and MXB 1730−335. A previous analysis based on BeppoSAX data of GRS 1915+105 revealed a hard-X delay (HXD), that is a lag of the burst rise at higher energies with respect to lower ones; this leads to narrower pulse widths, w, at higher energies. We here use some light curves of Rossi-XTE observations of GRS 1915+105 for a deeper analysis of this effect and search for its presence in those extracted from some IGR J17091−3624 and MXB 1730−335 observations performed with the same satellite. Our results show that, at variance with GRS 1915+105, no HXD is evident in the light curves of MXB 1730−335 and only a marginal HXD may be argued for IGR J17091−3624. For GRS 1915+105 we find a decreasing trend of the pulse width with energy following a power law w = A ⋅ E−s with an index s ≈ 0.8. Furthermore, we confirm the increase of the HXD with the recurrence time Trec of the bursts in each series that was already found in previous works using BeppoSAX data. Based on a spectral analysis of these three sources we conclude that the differences highlighted in the properties of the “heartbeat” variability are probably related to the different accreting compact object and the eventual presence of a corona in these binary interacting systems.
Substituent Effects of 2-Pyridones on Selective O-Arylation with Diaryliodonium Salts: Synthesis of 2-Aryloxypyridines under Transition­-Metal-Free Conditions
Authors: Mo Dong-Liang , Li Xiao-Hua , Ye Ai-Hui , Liang Cui
Published: January 2018

An efficient transition-metal-free strategy to synthesize 2-aryloxypyridine derivatives has been developed by a selective O-arylation of 2-pyridones with diaryliodonium salts. The reaction was compatible with a series of functional groups for 2-pyridones and diaryliodonium salts such as halides, nitro, cyano, and ester groups. The substituents at the C6-position of 2-pyridones favored O-arylation products because of steric hindrance. The reaction was easily performed on a gram-scale and 6-chloro-2-pyridone was a good precursor to access various unsubstituted 2-aryloxypyridines by dehalogenation. A P2Y1 lead compound analogue could be prepared in good yield over two steps.
Improved Synthesis of Glucosinolates
Authors: Hewitt Russell , Lim Yi , Ong Michelle
Published: January 2018

Herein we describe an improved synthesis of glucosinolates, in which the quantity and cost of materials have been reduced by approximately an order of magnitude compared to typical literature procedures. This allowed us to produce multiple glucosinolates in 10–25 gram batches using vessel sizes no larger than 0.5 litres.
Diagnostics of microwave assisted electron cyclotron resonance plasma source for surface modification of nylon 6
Authors: More Supriya E. , Das Partha Sarathi , Bansode Avinash , Dhamale Gayatri , Ghorui S. , Bhoraskar S. V. , Sahasrabudhe S. N. , Mathe Vikas L.
Published: January 2018

Looking at the increasing scope of plasma processing of materials surface, here we present the development and diagnostics of a microwave assisted Electron Cyclotron Resonance (ECR) plasma system suitable for surface modification of polymers. Prior to the surface-treatment, a detailed diagnostic mapping of the plasma parameters throughout the reactor chamber was carried out by using single and double Langmuir probe measurements in Ar plasma. Conventional analysis of I-V curves as well as the elucidation form of the Electron Energy Distribution Function (EEDF) has become the source of calibration of plasma parameters in the reaction chamber. The high energy tail in the EEDF of electron temperature is seen to extend beyond 60 eV, at much larger distances from the ECR zone. This proves the suitability of the rector for plasma processing, since the electron energy is much beyond the threshold energy of bond breaking in most of the polymers. Nylon 6 is used as a representative candidate for surface processing in the presence of Ar, H2 + N2, and O2 plasma, treated at different locations inside the plasma chamber. In a typical case, the work of adhesion is seen to almost get doubled when treated with oxygen plasma. Morphology of the plasma treated surface and its hydrophilicity are discussed in view of the variation in electron density and electron temperature at these locations. Nano-protrusions arising from plasma treatment are set to be responsible for the hydrophobicity. Chemical sputtering and physical sputtering are seen to influence the surface morphology on account of sufficient electron energies and increased plasma potential.
Design of spoke type motor and magnetizer for improving efficiency based rare-earth-free permanent-magnet motor
Authors: Kim Young Hyun , Cheon Byung Chul , Lee Jung Ho
Published: January 2018

This study proposes criteria for both optimal-shape and magnetizer-system designs to be used for a high-output spoke-type motor. The study also examines methods of reducing high-cogging torque and torque ripple, to prevent noise and vibration. The optimal design of the stator and rotor can be enhanced using both a response surface method and finite element method. In addition, a magnetizer system is optimally designed for the magnetization of permanent magnets for use in the motor. Finally, this study verifies that the proposed motor can efficiently replace interior permanent magnet synchronous motor in many industries.
Nanoscopic insights into the effect of silicon on core-shell InGaN/GaN nanorods: Luminescence, composition, and structure
Authors: Ren Christopher X. , Tang Fengzai , Oliver Rachel A. , Zhu Tongtong
Published: January 2018

GaN-based nanorods and nanowires have recently shown great potential as a platform for future energy-efficient photonic and optoelectronic applications, such as light emitting diodes and nanolasers. Currently, the most industrially scalable method of growing III-nitride nanorods remains metal-organic vapour phase epitaxy: whilst this growth method is often used in conjunction with extrinsic metallic catalyst particles, these particles can introduce unwanted artifacts in the nanorods such as stacking faults. In this paper, we examine the catalyst-free growth of GaN/InGaN core-shell nanorods by metal-organic vapor phase epitaxy for optoelectronic applications using silane to enhance the vertical growth of the nanorods. We find that both the silane concentration and exposure time can greatly affect the nanorod properties, and that larger concentrations and longer exposure times can severely degrade the nanorod structure and thus result in reduced emission from the InGaN QW shell. Finally, we report that the mechanism behind the effect of silane on the nanorod structure is the unintentional formation of an SiNx interlayer following completion of the growth of the nanorod core. This interlayer induces the growth of GaN islands on the nanorod sidewalls, the spatial distribution of which can affect their subsequent coalescence during the lateral growth stages and result in non-uniformity in the nanorod structure. This suggests that careful control of the silane flow must be exerted during growth to achieve both high aspect ratio nanorods and uniform emission along the length of the nanorod.
Dynamic coarse-graining fills the gap between atomistic simulations and experimental investigations of mechanical unfolding
Authors: Knoch Fabian , Schäfer Ken , Diezemann Gregor , Speck Thomas
Published: January 2018

We present a dynamic coarse-graining technique that allows one to simulate the mechanical unfolding of biomolecules or molecular complexes on experimentally relevant time scales. It is based on Markov state models (MSMs), which we construct from molecular dynamics simulations using the pulling coordinate as an order parameter. We obtain a sequence of MSMs as a function of the discretized pulling coordinate, and the pulling process is modeled by switching among the MSMs according to the protocol applied to unfold the complex. This way we cover seven orders of magnitude in pulling speed. In the region of rapid pulling, we additionally perform steered molecular dynamics simulations and find excellent agreement between the results of the fully atomistic and the dynamically coarse-grained simulations. Our technique allows the determination of the rates of mechanical unfolding in a dynamical range from approximately 10−8/ns to 1/ns thus reaching experimentally accessible time regimes without abandoning atomistic resolution.
Nonlocal boundary conditions for corrugated acoustic metasurface with strong near-field interactions
Authors: Schwan Logan , Umnova Olga , Boutin Claude , Groby Jean-Philippe
Published: January 2018

The propagation of long-wavelength sound in the presence of a metasurface made by arranging acoustic resonators periodically upon or slightly above an impervious substrate is studied. The method of two-scale asymptotic homogenization is used to derive effective boundary conditions, which account for both the surface corrugation and the low-frequency resonance. This method is applied to periodic arrays of resonators of any shape operating in the long-wavelength regime. The approach relies on the existence of a locally periodic boundary layer developed in the vicinity of the metasurface, where strong near-field interactions of the resonators with each other and with the substrate take place. These local effects give rise to an effective surface admittance supplemented by nonlocal contributions from the simple and double gradients of the pressure at the surface. These phenomena are illustrated for the periodic array of cylindrical Helmholtz resonators with an extended inner duct. Effects of the centre-to-centre spacing and orientation of the resonators' opening on the nonlocality and apparent resonance frequency are studied. The model could be used to design metasurfaces with specific effective boundary conditions required for particular applications.
Effects of stray lights on Faraday rotation measurement for polarimeter-interferometer system on EAST
Authors: Zou Z. Y. , Liu H. Q. , Ding W. X. , Chen J. , Brower D. L. , Lian H. , Wang S. X. , Li W. M. , Yao Y. , Zeng L. , Jie Y. X.
Published: January 2018

A double-pass radially view 11 chords polarimeter-interferometer system has been operated on the experimental advanced superconducting tokamak and provides important current profile information for plasma control. Stray light originating from spurious reflections along the optical path (unwanted reflections from various optical components/mounts and transmissive optical elements such as windows, waveplates, and lens as well as the detectors) and also direct feedback from the retro-reflector used to realize the double-pass configuration can both contribute to contamination of the Faraday rotation measurement accuracy. Modulation of the Faraday rotation signal due to the interference from multiple reflections is observable when the interferometer phase (plasma density) varies with time. Direct reflection from the detector itself can be suppressed by employing an optical isolator consisting of a λ/4-waveplate and polarizer positioned in front of the mixer. A Faraday angle oscillation during the density ramping up (or down) can be reduced from 5°–10° to 1°–2° by eliminating reflections from the detector. Residual modulation arising from misalignment and stray light from other sources must be minimized to achieve accurate measurements of Faraday rotation.
Active vs. spectator modes in nonadiabatic photodissociation dynamics of the hydroxymethyl radical via the 22A(3s) Rydberg state
Authors: Xie Changjian , Guo Hua
Published: January 2018

The choice of the active degrees of freedom (DOFs) is a pivotal issue in a reduced-dimensional model of quantum dynamics when a full-dimensional one is not feasible. Here, several five-dimensional (5D) models are used to investigate the nonadiabatic photodissociation dynamics of the hydroxymethyl (CH2OH) radical, which possesses nine internal DOFs, in its lowest absorption band. A normal-mode based scheme is used to identify the active and spectator modes, and its predictions are confirmed by 5D quantum dynamical calculations. Our results underscore the important role of the CO stretching mode in the photodissociation dynamics of CH2OH, originating from the photo-induced promotion of an electron from the half-occupied π*CO antibonding orbital to a carbon Rydberg orbital.
Iron and intrinsic deep level states in Ga2O3
Authors: Ingebrigtsen M. E. , Varley J. B. , Kuznetsov A. Yu. , Svensson B. G. , Alfieri G. , Mihaila A. , Badstübner U. , Vines L.
Published: January 2018

Using a combination of deep level transient spectroscopy, secondary ion mass spectrometry, proton irradiation, and hybrid functional calculations, we identify two similar deep levels that are associated with Fe impurities and intrinsic defects in bulk crystals and molecular beam epitaxy and hydride vapor phase epitaxi-grown epilayers of β-Ga2O3. First, our results indicate that FeGa, and not an intrinsic defect, acts as the deep acceptor responsible for the often dominating E2 level at ∼0.78 eV below the conduction band minimum. Second, by provoking additional intrinsic defect generation via proton irradiation, we identified the emergence of a new level, labeled as E2*, having the ionization energy very close to that of E2, but exhibiting an order of magnitude larger capture cross section. Importantly, the properties of E2* are found to be consistent with its intrinsic origin. As such, contradictory opinions of a long standing literature debate on either extrinsic or intrinsic origin of the deep acceptor in question converge accounting for possible contributions from E2 and E2* in different experimental conditions.
On necessary conditions for the comparison principle and the sub- and supersolution method for the stationary Kirchhoff equation
Authors: Iturriaga Leonelo , Massa Eugenio
Published: January 2018

In this paper, we propose a counterexample to the validity of the comparison principle and of the sub- and supersolution method for nonlocal problems like the stationary Kirchhoff equation. This counterexample shows that in general smooth bounded domains in any dimension, these properties cannot hold true if the nonlinear nonlocal term M(u2) is somewhere increasing with respect to the H01-norm of the solution. Comparing with the existing results, this fills a gap between known conditions on M that guarantee or prevent these properties and leads to a condition that is necessary and sufficient for the validity of the comparison principle. It is worth noting that equations similar to the one considered here have gained interest recently for appearing in models of thermo-convective flows of non-Newtonian fluids or of electrorheological fluids, among others.
Photoelectron Spectroscopic Study of Methanol Adsorbed Rutile TiO2(110) Surface
Authors: Hao Qun-qing , Wang Zhi-qiang , Dai Dong-xu , Zhou Chuan-yao , Yang Xue-ming
Published: January 2018

Methanol/TiO2(110) is a model system in the surface science study of photocatalysis where methanol is taken as a hole capture. However, the highest occupied molecular orbital of adsorbed methanol lies below the valence band maximum of TiO2, preventing the hole transfer. To study the level alignment of this system, electronic structure of methanol covered TiO2(110) surface has been measured by ultraviolet photoelectron spectroscopy and the molecular orbitals of adsorbed methanol have been clearly identified. The results indicate the weak interaction between methanol and TiO2 substrate. The static electronic structure also suggests the mismatch of the energy levels. These static experiments have been performed without band gap excitation which is the prerequisite of a photocatalytic process. Future study of the transient electronic structure using time-resolved UPS has also been discussed.
The microstructure and mechanical properties of as-cast Mg–4Y/Nd–2Zn alloys
Authors: Liu Yang , Liu Xiqin , Liu Zili , Liu Guodong , Fan Ruyou , Yin Han , Li Jian
Published: January 2018

Optical microscopy, scanning electron microscopy, X-ray diffraction and tensile testing were performed to investigate the microstructure and mechanical properties of as-cast Mg–4Y/Nd–2Zn alloys. The results show that the secondary dendritic arm spacing for the Mg–4Y–2Zn alloy is smaller than that for the Mg–4Nd–2Zn alloy, and that X-Mg12YZn or W-Mg3Zn3Nd2 form in Mg–4Y/Nd–2Zn alloys. The lamellar X phase distributes at the grain boundary, pointing into the grains, whereas the rod-like W phase preferentially segregates at the triangle junction of the grain boundary. The greater grain boundary strengthening effect and the smaller fragmentation effect of the brittle eutectic phases leads to the as-cast Mg–4Y–2Zn alloy having better comprehensive mechanical properties. The fracture mechanism for as-cast Mg–4Y/Nd–2Zn alloys is quasi-cleavage fracture.
The relationship between meeting of recommendations on physical activity for health and perceived work ability among white‐collar workers
Authors: Nawrocka Agnieszka , Garbaciak Wiesław , Cholewa Jarosław , Mynarski Władysław
Published: January 2018

Objective: The aim of this study was to evaluate the association between meeting recommendations on physical activity for health in leisure‐time and the ability to work among Polish white‐collar workers. Methods: The study used a cross‐sectional design with a convenience sample of 360 white‐collar workers. Participants recorded 7‐day physical activity logs, including form, duration and intensity of leisure‐time physical activities. The results were compared to health recommendations. A standardized Work Ability Index (WAI) questionnaire was used in assessing the ability to work. Results: Participants who met health recommendations achieved higher scores of the WAI (mean score = 41.93) in comparison to those who were not sufficiently physically active (mean score = 39.35) (p < .001). The results of binary logistic regression show that meeting health‐related physical activity recommendations almost double the odds of reaching at least good work ability (OR = 1.94, 95% CI = 1.12–3.36). Conclusions: Meeting leisure‐time physical activity recommendations (especially the criterion of vigorous physical activity) is significantly related to higher self‐assessed ability to work among white‐collar workers.
Sodium bicarbonate ingestion increases glycolytic contribution and improves performance during simulated taekwondo combat
Authors: Lopes‐Silva João Paulo , Da Silva Santos Jonatas Ferreira , Artioli Guilherme Giannini , Loturco Irineu , Abbiss Chris , Franchini Emerson
Published: January 2018

Purpose: To investigate the effect of sodium bicarbonate (NaHCO3) on performance and estimated energy system contribution during simulated taekwondo combat. Methods: Nine taekwondo athletes completed two experimental sessions separated by at least 48 h. Athletes consumed 300 mg/kg body mass of NaHCO3 or placebo (CaCO3) 90 min before the combat simulation (three rounds of 2 min separated by 1 min passive recovery), in a double‐blind, randomized, repeated‐measures crossover design. All simulated combat was filmed to quantify the time spent fighting in each round. Lactate concentration [La−] and rating of perceived exertion (RPE) were measured before and after each round, whereas heart rate (HR) and the estimated contribution of the oxidative (WOXI), ATP (adenosine triphosphate)‐phosphocreatine (PCr) (WPCR), and glycolytic systems were calculated during the combat simulation. Results: [La−] increased significantly after NaHCO3 ingestion, when compared with the placebo condition (+14%, P = 0.04, d = 3.70). NaHCO3 ingestion resulted in greater estimated glycolytic energy contribution in the first round when compared with the placebo condition (+31%, P = 0.01, d = 3.48). Total attack time was significantly greater after NaHCO3 when compared with placebo (+13%, P = 0.05, d = 1.15). WOXI, WPCR, VO2, HR and RPE were not different between conditions (P > 0.05). Conclusion: NaHCO3 ingestion was able to increase the contribution of glycolytic metabolism and, therefore, improve performance during simulated taekwondo combat.
Giardia secretome highlights secreted tenascins as a key component of pathogenesis
Authors: Dubourg Audrey , Xia Dong , Winpenny John P , Al Naimi Suha , Bouzid Maha , Sexton Darren W , Wastling Jonathan M , Hunter Paul R , Tyler Kevin M
Published: January 2018

Background

Giardia is a protozoan parasite of public health relevance that causes gastroenteritis in a wide range of hosts. Two genetically distinct lineages (assemblages A and B) are responsible for the human disease. Although it is clear that differences in virulence occur, the pathogenesis and virulence of Giardia remain poorly understood.

Results

The genome of Giardia is believed to contain open reading frames that could encode as many as 6000 proteins. By successfully applying quantitative proteomic analyses to the whole parasite and to the supernatants derived from parasite culture of assemblages A and B, we confirm expression of ~1600 proteins from each assemblage, the vast majority of which are common to both lineages. To look for signature enrichment of secreted proteins, we considered the ratio of proteins in the supernatant compared with the pellet, which defined a small group of enriched proteins, putatively secreted at a steady state by cultured growing trophozoites of both assemblages. This secretome is enriched with proteins annotated to have N-terminal signal peptide. The most abundant secreted proteins include known virulence factors such as cathepsin B cysteine proteases and members of a Giardia superfamily of cysteine-rich proteins that comprise variant surface proteins, high-cysteine membrane proteins, and a new class of virulence factors, the Giardia tenascins. We demonstrate that physiological function of human enteric epithelial cells is disrupted by such soluble factors even in the absence of the trophozoites.

Conclusions

We are able to propose a straightforward model of Giardia pathogenesis incorporating key roles for the major Giardia-derived soluble mediators.
Non-B-Form DNA Is Enriched at Centromeres
Authors: Kasinathan Sivakanthan , Henikoff Steven
Published: January 2018

Animal and plant centromeres are embedded in repetitive “satellite” DNA, but are thought to be epigenetically specified. To define genetic characteristics of centromeres, we surveyed satellite DNA from diverse eukaryotes and identified variation in <10-bp dyad symmetries predicted to adopt non-B-form conformations. Organisms lacking centromeric dyad symmetries had binding sites for sequence-specific DNA-binding proteins with DNA-bending activity. For example, human and mouse centromeres are depleted for dyad symmetries, but are enriched for non-B-form DNA and are associated with binding sites for the conserved DNA-binding protein CENP-B, which is required for artificial centromere function but is paradoxically nonessential. We also detected dyad symmetries and predicted non-B-form DNA structures at neocentromeres, which form at ectopic loci. We propose that centromeres form at non-B-form DNA because of dyad symmetries or are strengthened by sequence-specific DNA binding proteins. This may resolve the CENP-B paradox and provide a general basis for centromere specification.
Evaluation of Stereotactic Radiotherapy of the Resection Cavity After Surgery of Brain Metastases Compared to Postoperative Whole-Brain Radiotherapy (ESTRON)—A Single-Center Prospective Randomized Trial
Authors: El Shafie Rami A , Paul Angela , Bernhardt Denise , Hauswald Henrik , Welzel Thomas , Sprave Tanja , Hommertgen Adriane , Krisam Johannes , Schmitt Daniela , Klüter Sebastian , Schubert Kai , Klose Christina , Kieser Meinhard , Debus Jürgen , Rieken Stefan
Published: January 2018

BACKGROUND

Neurosurgical resection is recommended for symptomatic brain metastases, in oligometastatic patients or for histology acquisition. Without adjuvant radiotherapy, roughly two-thirds of the patients relapse at the resection site within 24 mo, while the risk of new metastases in the untreated brain is around 50%. Adjuvant whole-brain radiotherapy (WBRT) can reduce the risk of both scenarios of recurrence significantly, although the associated neurocognitive toxicity is substantial, while stereotactic radiotherapy (SRT) improves local control at comparably low toxicity.

OBJECTIVE

To compare locoregional control and treatment-associated toxicity for postoperative SRT and WBRT after the resection of 1 brain metastasis in a single-center prospective randomized study.

METHODS

Fifty patients will be randomized to receive either hypofractionated SRT of the resection cavity and single- or multisession SRT of all unresected brain metastases (up to 10 lesions) or WBRT. Patients will be followed-up regularly and the primary endpoint of neurological progression-free survival will be assessed by magnetic resonance imaging (MRI). Quality of life and neurocognition will be assessed in 3-mo intervals using standardized tests and EORTC questionnaires.

EXPECTED OUTCOMES

We expect to show that postoperative SRT of the resection cavity and further unresected brain metastases is a valid means of improving locoregional control over observation at less neurocognitive toxicity than caused by WBRT.

DISCUSSION

The present study is the first to compare locoregional control as well as neurocognitive toxicity for postoperative SRT and WBRT in patients with up to 10 metastases, while utilizing a highly sensitive and standardized MRI protocol for treatment planning and follow-up.
Robotic Radiosurgery for Brain Metastases Diagnosed With Either SPACE or MPRAGE Sequence (CYBER-SPACE)—A Single-Center Prospective Randomized Trial
Authors: El Shafie Rami A , Paul Angela , Bernhardt Denise , Lang Kristin , Welzel Thomas , Sprave Tanja , Hommertgen Adriane , Krisam Johannes , Schmitt Daniela , Klüter Sebastian , Schubert Kai , Klose Christina , Kieser Meinhard , Debus Jürgen , Rieken Stefan
Published: January 2018

BACKGROUND

Stereotactic radiosurgery (SRS) of brain metastases (BM) is recommended in oligometastatic scenarios as a less toxic treatment alternative to whole-brain radiotherapy. Recent findings support SRS for patients with multiple (>3) BM. Furthermore, advances in MR imaging have facilitated the detection of very small BM, as advances in SRS technology have facilitated the highly conformal and simultaneous treatment of multiple target lesions.

OBJECTIVE

To compare efficacy and toxicity of repeated frameless robotic SRS of up to 10 simultaneous BM through a single-center prospective randomized trial.

METHODS

Two hundred patients will be randomized and receive imaging and treatment based on either the highly sensitive SPACE (sampling perfection with application optimized contrasts using different flip angle evolution) or the MPRAGE (magnetization-prepared rapid gradient-echo) magnetic resonance imaging sequence. If during follow-up new metastases are detected, treatment is repeated. The primary endpoint is reached when a patient develops more than 10 simultaneous new BM and is thus deemed unsuitable for further SRS. Overall survival will be assessed as secondary endpoint. Quality of life and neurocognition will be evaluated every 3 mo using CANTAB tests and EORTC (European Organisation for Research and Treatment of Cancer) questionnaires.

EXPECTED OUTCOMES

We expect to show that repeated SRS based on sensitive imaging can delay intracranial dissemination while preserving neurocognitive function and quality of life.

DISCUSSION

The present study is the first to prospectively assess the benefit of sensitive imaging and repeated stereotactic irradiation in the treatment of patients with multiple BM. It represents a novel approach, where in a palliative setting advanced technology in treatment and diagnostics is employed to improve tumor control while also reducing toxicity and preserving quality of life.
Internal Carotid Artery Bifurcation Aneurysms: Microsurgical Strategies and Operative Nuances for Different Aneurysmal Directions
Authors: Savardekar Amey R , Patra Devi Prasad , Narayan Vinayak , Bollam Papireddy , Guthikonda Bharat , Nanda Anil
Published: January 2018

BACKGROUND

Internal carotid artery bifurcation aneurysms (ICAbifAs), comprising approximately 5% of intracranial aneurysms, are characterized clinically by their tendency to occur at a younger age and surgically by the technical difficulties posed by their domes being adherent to the frontal lobe, their location at the apex of the sylvian fissure, and their relation to myriad perforator complexes.

OBJECTIVE

To review the nuances of technique and operative strategy specific to aneurysmal direction in the light of our experience with ICAbifAs.

METHODS

ICAbifAs managed at our institute from January 2001 to July 2016 were analyzed. Detailed analysis of clinical data, pre- and postoperative radiology, operative notes and videos, and clinical outcome was done.

RESULTS

Fifty-one patients with ICAbifAs were treated in the study period out of which 40 patients underwent microsurgical clipping. The median age was 48 yr (range 14-68 yr). Nearly 95% of the patients presented in a good clinical grade (World Federation of Neurological Surgeons grade 1 and 2). At 6-mo follow-up, 36 patients (90%) had good clinical outcome (Glasgow Outcome Scale 4 and 5). According to their direction, ICAbifAs were grouped as anteriorly directed (10 cases), superiorly directed (23 cases), and posteriorly directed (7 cases). Operative techniques and nuances utilized depend on aneurysmal direction and are presented here.

CONCLUSION

An appropriate surgical strategy based on the direction of ICAbifAs as per the preoperative radiology, meticulous dissection of aneurysmal wall from adjacent perforators, and clip application with the aim of remodeling the ICA bifurcation are integral to achieving a good outcome.
MACULAR ATROPHY INCIDENCE IN ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR–TREATED NEOVASCULAR AGE-RELATED MACULAR DEGENERATION
Authors: Mantel Irmela , Dirani Ali , Zola Marta , Parvin Parmis , De Massougnes Sophie , Bergin Ciara
Published: January 2018

Purpose:

To investigate factors associated with macular atrophy (MA) incidence in neovascular age-related macular degeneration treated with either ranibizumab or aflibercept in an Observe-and-Plan variable dosing regimen.

Methods:

Information was obtained from two identical prospective treatment protocols using ranibizumab or aflibercept in a variable dosing regimen termed “Observe and Plan.” Eyes without MA at baseline were included. New atrophy at the final 2-year visit was investigated with univariate and multivariate analysis to identify associated risk factors, focusing on treatment factors.

Results:

De novo MA developed in 63 (42%) of 149 eyes/patients (mean age 79.0 years), in 70 eyes treated using aflibercept and 79 eyes using ranibizumab. The univariate analysis showed multiple associations of MA with baseline factors, of which the following were confirmed as independent risk factors after multivariate stepwise logistic regression: lower number of anti–vascular endothelial growth factors injections (P = 0.011), depigmentation (P = 0.0004), reticular pseudodrusen (P = 0.0005), lower baseline visual acuity (P = 0.0006), and retinal angiomatous proliferation (P = 0.001). The drug type showed no significant association with MA incidence (P = 0.21).

Conclusion:

Within the variable dosing regimen, MA incidence was higher when fewer injections were required. More injections, if required by disease activity, did not increase the risk for MA.
Association of aortic valve disease with intestinal angioectasia: data from the Nationwide Inpatient Sample
Authors: Jehangir Asad , Pathak Ranjan , Ukaigwe Anene , Donato Anthony A.
Published: January 2018

Objective

Since the description of a correlation between aortic stenosis and angioectasia, controversy has persisted about whether these diseases are truly associated or coincidental findings of older age. Our objective was to determine the association of aortic valve disease and bleeding intestinal angioectasia from a large database.

Patients and methods

We used the 2011 Nationwide Inpatient Sample database to identify hospitalizations in the USA in patients with bleeding intestinal angioectasia. International Classification of Diseases, 9th revision, Clinical Modification codes were used to identify patients with aortic valve disease, mitral valve disease, and known risk factors for angioectasia (including diagnosed von Willebrand disease, left ventricular assist device, and chronic kidney disease). Univariate and multivariate logistic regression were used to determine the odds of association between the valvular diseases and angioectasia.

Results

A total of 32 079 intestinal angioectasia-related hospitalizations were identified of which 7.02% (n=2253) cases had coexistent aortic valve disease. The unadjusted odds of aortic valve disease in association with bleeding intestinal angioectasia versus those without bleeding angioectasia was 4.95 [95% confidence interval: (CI): 4.43–5.54, P<0.001]. The association of intestinal angioectasia with mitral valve disease was not significant (odds ratio=1.56, 95% CI: 0.59–4.14, P=0.38). When adjusted for age and known risk factors, the odds of aortic valve disease in bleeding intestinal angioectasia was still significant (odds ratio=2.37, 95% CI: 2.10–2.66, P<0.001).

Conclusion

Our findings support an important association between aortic valve disease and bleeding intestinal angioectasia, not identified in valvular heart valvular diseases with lower shear stress (mitral valve disease).
Development and Validity Testing of an Arthritis Self-Management Assessment Tool
Authors: Oh HyunSoo , Han SunYoung , Kim SooHyun , Seo WhaSook
Published: January 2018

BACKGROUND:

Because of the chronic, progressive nature of arthritis and the substantial effects it has on quality of life, patients may benefit from self-management. However, no valid, reliable self-management assessment tool has been devised for patients with arthritis.

PURPOSE:

This study was conducted to develop a comprehensive self-management assessment tool for patients with arthritis, that is, the Arthritis Self-Management Assessment Tool (ASMAT).

METHODS:

To develop a list of qualified items corresponding to the conceptual definitions and attributes of arthritis self-management, a measurement model was established on the basis of theoretical and empirical foundations. Content validity testing was conducted to evaluate whether listed items were suitable for assessing arthritis self-management. Construct validity and reliability of the ASMAT were tested. Construct validity was examined using confirmatory factor analysis and nomological validity.

RESULTS:

The 32-item ASMAT was developed with a sample composed of patients in a clinic in South Korea. Content validity testing validated the 32 items, which comprised medical (10 items), behavioral (13 items), and psychoemotional (9 items) management subscales. Construct validity testing of the ASMAT showed that the 32 items properly corresponded with conceptual constructs of arthritis self-management, and were suitable for assessing self-management ability in patients with arthritis. Reliability was also well supported.

CONCLUSION:

The ASMAT devised in the present study may aid the evaluation of patient self-management ability and the effectiveness of self-management interventions. The authors believe the developed tool may also aid the identification of problems associated with the adoption of self-management practice, and thus improve symptom management, independence, and quality of life of patients with arthritis.
A Systematic Integrative Review of Pin Site Crusts
Authors: Georgiades Dimitra-Simone
Published: January 2018

There continues to be a lack of knowledge in the overall management of pin site crusts for orthopaedic clinicians to make evidence-based decisions on their retention or removal. The goal of pin site care is to reduce, or where possible, prevent pin site infection. Understanding the role of pin site crusts in the management of the pin site and prevention of pin site infection is important. The aim of this systematic integrative review is to explore the effectiveness of pin site crusts as a biological dressing versus the removal of pin site crusts in pin site care and prevention of pin site infection. Three electronic databases were used to conduct a systematic search. The methodologies of five studies that met inclusion criteria were appraised using the Mixed Method appraisal Tool. Findings reveal that pin site crusts have similar properties to that of a dressing, as the crusts are able to act as a barrier between the insertion site of the pin and external environment, which can reduce infection. Additional high-quality evidence is required to solidify the effectiveness of pin site crusts as a biological dressing.
Laparoscopic Hilar Lymph Node Sampling in Patients With Biliary Tract Cancers That are Rarely Associated With Nodal Metastasis
Authors: Kobayashi Shogo , Tomokuni Akira , Takahashi Hidenori , Akita Hirofumi , Marubashi Shigeru , Gotoh Kunihito , Yanagimoto Yoshitomo , Takahashi Yusuke , Sugimura Keijiro , Miyoshi Norikatsu , Moon Jeong Ho , Yasui Masayoshi , Omori Takeshi , Miyata Hiroshi , Ohue Masayuki , Fujiwara Yoshiyuki , Yano Masahiko , Sakon Masato
Published: January 2018

Purpose:

Among the various types of biliary tract cancer, patients with single, small (<5 cm), peripheral intrahepatic cholangiocarcinoma (ICC), or small (<2 cm) gallbladder tumors (GBTs) rarely develop lymph node (LN) metastasis. We investigated a laparoscopic approach for hilar LN sampling in such cases.

Methods:

Among the 176 patients with biliary tract cancer who were treated from January 2012 to March 2017, 21 (ICC, n=4; GBT, n=17) met the above indications.

Results:

All patients were treated by a laparoscopic approach with R0 resection. After determining the pathologic diagnosis, 9 patients with GBT and all 4 patients with ICC underwent laparoscopic LN sampling; the mean numbers of sampled LNs were 2.6 and 7.3, respectively; no patients had metastasis. The mean operating times for GBT and ICC were 223 and 379 minutes, respectively; the mean blood loss was 23 mL and 171 mL. With the exception of 1 patient who developed intrahepatic metastasis of ICC at the opposite liver lobe, all of the patients were recurrence free.

Conclusions:

A laparoscopic approach could be safely applied under our indications.
Vitamin E Supplementation in Pediatric Nonalcoholic Fatty Liver Disease
Authors: Patusco Rachael , Zelig Rena , Parker Anna
Published: January 2018

Nonalcoholic fatty liver disease is the most common type of liver disease seen in children. Development and progression of the disease are linked to oxidative injury and stress. Improving antioxidant-oxidant balance as an interventional strategy for the management and treatment of pediatric nonalcoholic fatty liver disease has been studied. Because of concerns of inadequate vitamin E consumption and status among children and adolescents, this review explores how supplemental vitamin E, in conjunction with lifestyle modification, can influence pediatric nonalcoholic fatty liver disease progression and treatment.
Synergistic binding of bHLH transcription factors to the promoter of the maize NADP-ME gene used in C4 photosynthesis is based on an ancient code found in the ancestral C3 state
Authors: Borba Ana Rita , Serra Tânia S. , Górska Alicja , Gouveia Paulo , Cordeiro André M. , Reyna-Llorens Ivan , Kneřová Jana , Barros Pedro M. , Abreu Isabel A. , Oliveira M. Margarida , Hibberd Julian M. , Saibo Nelson J.M.
Published: January 2018

C4 photosynthesis has evolved repeatedly from the ancestral C3 state to generate a carbon concentrating mechanism that increases photosynthetic efficiency. This specialised form of photosynthesis is particularly common in the PACMAD clade of grasses, and is used by many of the world’s most productive crops. The C4 cycle is accomplished through cell-type specific accumulation of enzymes but cis-elements and transcription factors controlling C4 photosynthesis remain largely unknown. Using the NADP-Malic Enzyme (NADP-ME) gene as a model we aimed to better understand molecular mechanisms associated with the evolution of C4 photosynthesis. Two basic Helix-Loop-Helix (bHLH) transcription factors, ZmbHLH128 and ZmbHLH129, were shown to bind the C4NADP-ME promoter from maize. These proteins form heterodimers and ZmbHLH129 impairs trans-activation by ZmbHLH128. Electrophoretic mobility shift assays indicate that a pair of cis-elements separated by a seven base pair spacer synergistically bind either ZmbHLH128 or ZmbHLH129. This pair of cis-elements is found in both C3 and C4 species of the PACMAD clade. Our analysis is consistent with this cis-element pair originating from a single motif present in the ancestral C3 state. We conclude that C4 photosynthesis has co-opted an ancient C3 regulatory code built on G-box recognition by bHLH to regulate the NADP-ME gene. More broadly, our findings also contribute to the understanding of gene regulatory networks controlling C4 photosynthesis.