bluuebunny/crossref_metadata_2025 huggingface dataset:
Renal clearable noble metal nanoparticles: photoluminescence, elimination, and biomedical applications
Authors: Xu Jing , Peng Chuanqi , Yu Mengxiao , Zheng Jie
Published: January 2017

Metal nanoparticles have demonstrated broad and promising biomedical applications in research laboratories, but how to fulfill their promises in the clinical practices demands extensive effort to minimize their non‐specific accumulation in the body. In the past 6 years, we have developed a class of renal clearable noble metal nanoparticles with tunable visible and near‐infrared emission, which can behave like small molecular contrast agents to be effectively eliminated through the kidneys. By taking advantage of the unique clearance pathway, we were able to gain some fundamental understanding of how engineering nanoparticles cleared out of the body through urinary system. Moreover, they also provided unique opportunities in early cancer detection and kidney functional imaging that were often challenging to be achieved with non‐renal clearable nanoparticles and small molecular probes. In this review, we summarize key factors that govern in the renal clearance of luminescent noble metal nanoparticles and their strengths in cancer targeting and kidney functional imaging. At the end, we also outline several key challenges that need to be addressed before they can be considered in the clinical practices. WIREs Nanomed Nanobiotechnol 2017, 9:e1453. doi: 10.1002/wnan.1453

This article is categorized under:

Diagnostic Tools > In Vivo Nanodiagnostics and Imaging
Compositional and microstructural study of joining methods in archaeological gold objects
Authors: Scrivano S. , Gómez Tubío B. , Ortega‐Feliu I. , Ager F. J. , Paul A. , Respaldiza M. A.
Published: January 2017

This work arises in response to the need to understand the production techniques of pre‐roman gold jewels, starting from the systematic characterization of the different methods of metal joining used in antiquity to produce these objects.

To meet this requirement, different procedures used in antiquity were reproduced by means of experimental archaeology. These models correspond to three metal‐joining methods reported by ancient recipes: solid‐state diffusion with copper salt, brazing and autogenous welding. These techniques were studied by different analytical methods in order to characterize them at both compositional and microstructural level (SEM‐EDS, metallography, μ‐XRF and μ‐PIXE). The results obtained show that the solid‐state diffusion bonding with copper salt presents a crystal hexagonal structure without phase changes in the joining point, where only a variation in the grain size is observed. At the compositional level, this soldering method is characterized by a local increase in copper concentration and a small decrease in gold content. In contrast, brazing shows a dendritic‐porous structure due to the superposition of the soldering alloy and the crystal structure of the original foils. Besides, the compositional analysis revealed an increment of silver and copper concentrations and a simultaneous reduction of gold concentration. Finally, in the autogenous welding, no changes at the microstructural and compositional levels were observed.

The results obtained have also demonstrated the usefulness of a portable μ‐XRF system for the in‐situ characterization of ancient jewels. Copyright © 2017 John Wiley & Sons, Ltd.
Proposing a Framework for Mobile Applications in Disaster Health Learning
Authors: Liu Alexander G. , Altman Brian A. , Schor Kenneth , Strauss-Riggs Kandra , Thomas Tracy N. , Sager Catherine , Leander-Griffith Michelle , Harp Victoria
Published: January 2017

Mobile applications, or apps, have gained widespread use with the advent of modern smartphone technologies. Previous research has been conducted in the use of mobile devices for learning. However, there is decidedly less research into the use of mobile apps for health learning (eg, patient self-monitoring, medical student learning). This deficiency in research on using apps in a learning context is especially severe in the disaster health field. The objectives of this article were to provide an overview of the current state of disaster health apps being used for learning, to situate the use of apps in a health learning context, and to adapt a learning framework for the use of mobile apps in the disaster health field. A systematic literature review was conducted by using the PRISMA checklist, and peer-reviewed articles found through the PubMed and CINAHL databases were examined. This resulted in 107 nonduplicative articles, which underwent a 3-phase review, culminating in a final selection of 17 articles. While several learning models were identified, none were sufficient as an app learning framework for the field. Therefore, we propose a learning framework to inform the use of mobile apps in disaster health learning. (Disaster Med Public Health Preparedness. 2017;11:487–495)
On Being in Hegel and Heidegger
Authors: Haas Andrew
Published: January 2017

What is being? This is, from the Greeks to Hegel (according to Heidegger), the guiding question of ontology and the history of philosophy as metaphysics. And the answer is presence: ‘being’ means ‘being present’, ‘presencing’; ‘to be’ means ‘to be present’. By clarifying the limit of this philosophy of presence, however, it is possible to go beyond it, to a thinking of being as presence and absence—for both coming-to-presence and going-out-into-absence are ways in which beings are, and being happens. And yet, are presence and absence the only ways to think being? On the contrary—there is a third. From the Greeks (through Hegel) to Heidegger, the being that fails to come to presence, but also does not simply remain in absence—this is what is merely implied, an implication. But then what does it mean to think being as implied? Being as implying? As an implication?
The Possibility of a Phenomenology of Cultural Worlds in Hegel and Husserl
Authors: Staehler Tanja
Published: January 2017

The world we live in proves best understood as a cultural world. Cultural worlds are examined in this article regarding their aesthetic and ethical dimensions, with the help of Hegel and Husserl. The ethical realm is characterized by a tension between ethical conscience and cultural norms. Even Hegel, who is often conceived as a philosopher of customs, explores the significance of conscience in a detailed phenomenology. Husserl provides a curious perspective on ethics when he, under the heading of a renewal (Japanese Kaizo) of reason, provides an account of a vaguely dialectical development of reason as logos which goes beyond the division between the ‘descriptive’ and ‘ethical’. In the wider sense of ethics, it is also ‘good’ to write about the world we live in. Literature (Hermann, Wallace) will be treated here as an exemplary art-form that stands in close proximity to philosophy since both strive to capture in language the world we live in.
Dietary calcium impairs tomato lycopene bioavailability in healthy humans
Authors: Borel Patrick , Desmarchelier C. , Dumont U. , Halimi C. , Lairon D. , Page D. , Sébédio J. L. , Buisson C. , Buffière C. , Rémond D.
Published: January 2017

Lycopene (LYC) bioavailability is relatively low and highly variable, because of the influence of several factors. Recent in vitro data have suggested that dietary Ca can impair LYC micellarisation, but there is no evidence whether this can lead to decreased LYC absorption efficiency in humans. Our objective was to assess whether a nutritional dose of Ca impairs dietary LYC bioavailability and to study the mechanism(s) involved. First, in a randomised, two-way cross-over study, ten healthy adults consumed either a test meal that provided 19-mg (all-E)-LYC from tomato paste or the same meal plus 500-mg calcium carbonate as a supplement. Plasma LYC concentration was measured at regular time intervals over 7 h postprandially. In a second approach, an in vitro digestion model was used to assess the effect of increasing Ca doses on LYC micellarisation and on the size and zeta potential of the mixed micelles produced during digestion of a complex food matrix. LYC bioavailability was diminished by 83 % following the addition of Ca in the test meal. In vitro, Ca affected neither LYC micellarisation nor mixed micelle size but it decreased the absolute value of their charge by 39 %. In conclusion, a nutritional dose of Ca can impair dietary LYC bioavailability in healthy humans. This inhibition could be due to the fact that Ca diminishes the electrical charge of micelles. These results call for a thorough assessment of the effects of Ca, or other divalent minerals, on the bioavailability of other carotenoids and lipophilic micronutrients.
Numerical Approximations to Extremal Toric Kähler Metrics with Arbitrary Kähler Class
Authors: Hall Stuart James , Murphy Thomas
Published: January 2017

We develop new algorithms for approximating extremal toric Kähler metrics. We focus on an extremal metric on , which is conformal to an Einstein metric (the Chen–LeBrun–Weber metric). We compare our approximation to one given by Bunch and Donaldson and compute various geometric quantities. In particular, we demonstrate a small eigenvalue of the scalar Laplacian of the Einstein metric that gives numerical evidence that the Einstein metric is conformally unstable under Ricci flow.
Endoscopic ear surgery: a hot topic?
Authors: Mitchell S , Coulson C
Published: January 2017

Objectives:

To summarise published research investigating maximal temperatures associated with endoscopes used in otology. Possible thermal issues surrounding the use of endoscopes in middle-ear surgery are discussed, and recommendations regarding the safest ways to use endoscopes in endoscopic ear surgery are made.

Methods:

A non-systematic review of the relevant literature was conducted, with descriptive analysis and presentation of the results.

Results:

There are currently no reports of any temperature-related deleterious effects in patients having undergone endoscopic ear surgery. There is debate regarding heat issues in endoscopic ear surgery, with a limited body of work documenting potential negative impacts of middle-ear heat exposure from endoscopes. The diameter of endoscope, type of light source used, distance from endoscope tip and duration of exposure are highlighted potential factors for high temperatures in endoscopic ear surgery.

Conclusion:

There is a trend towards endoscopes being used routinely in ear surgery. Simple practice points are recommended to minimise potential thermal risks.
Role of circumferential subannular tympanoplasty in anterior and subtotal perforations
Authors: Singh G B , Ranjan S , Arora R , Kumar S
Published: January 2017

Objective:

This study aimed to evaluate the surgical success of a modified inlay tympanoplasty technique, known as circumferential subannular tympanoplasty, for anterior and subtotal perforations.

Methods:

This prospective study was performed in a tertiary care teaching hospital between October 2013 and April 2016. A total of 58 adult patients of both sexes with anterior or subtotal perforations underwent circumferential subannular tympanoplasty under local anaesthesia. In this technique, after tympanomeatal flap elevation, the temporalis fascia graft is placed directly onto the annulus instead of being tucked underneath the tympanic membrane remnant. Outcome data were graft uptake and hearing improvement.

Results:

This technique had a surgical success rate of 97 per cent and led to significant hearing improvement.

Conclusion:

Circumferential subannular tympanoplasty has a definitive role in managing anterior and subtotal perforations.
Validation of a new ENT emergencies course for first-on-call doctors
Authors: Swords C , Smith M E , Wasson J D , Qayyum A , Tysome J R
Published: January 2017

Background:

First-on-call ENT cover is often provided by junior doctors with limited ENT experience; yet, they may have to manage life-threatening emergencies. An intensive 1-day simulation course was developed to teach required skills to junior doctors.

Methods:

A prospective, single-blinded design was used. Thirty-seven participants rated their confidence before the course, immediately following the course and after a two-month interval. Blinded assessors scored participant performance in two video-recorded simulated scenarios before and after the course.

Results:

Participant self-rated confidence was increased in the end-of-course survey (score of 27.5 vs 53.0; p < 0.0001), and this was maintained two to four months after the course (score of 50.5; p < 0.0001). Patient assessment and management in video-recorded emergency scenarios was significantly improved following course completion (score of 9.75 vs 18.75; p = 0.0093).

Conclusion:

This course represents an effective method of teaching ENT emergency management to junior doctors. ENT induction programmes benefit from the incorporation of a simulation component.
Upper Sorbian
Authors: Howson Phil
Published: January 2017

Sorbian is a West Slavic language spoken in eastern Germany, in Saxony and Brandenburg near the borders of Poland and the Czech Republic, and is recognized as an endangered language by UNESCO (Moseley 2012). It is commonly referred to as Sorbian in English, but has historically been referred to as both Wendish and Lusatian. The Sorbian speech area used to expand from its northernmost point approximately 50 km south-east of Berlin to its southernmost point approximately 8 km from the borders of the Czech Republic (Stone 1993). This area is also referred to as Lusatia (Figure 1). However, the Sorbian-speaking area continues to shrink every year and is currently much smaller than Stone (1993) describes. Upper Sorbian is currently only used in daily communication in and immediately around Budyšin (personal communication, Lechosław Jocz).
Performativity and Nomadic Subjectivity in Shobana Jeyasingh's TooMortal
Authors: Nijhawan Amita
Published: January 2017

In Shobana Jeyasingh's TooMortal, a contemporary dance piece made for historic churches in Britain and Europe, six dancers enact rituals of life's journey. They use the pews as coffins and cradles and in doing so they interact with the architecture and rituals of the church space in new and disruptive ways. In this article Amita Nijhawan utilizes Judith Butler's notion of performativity and Rosi Braidotti's concept of nomadic subjectivity to suggest that through these encounters the dancers construct the church as a space where women can find power, refuge, agency, and perhaps sensuality. The dancers start by engaging with church rituals and imperfectly reiterating them in such a way that the performance takes on a performative function. The dancers’ bodies show the potential for dancing female bodies to disrupt patriarchal spaces and, therefore, the normative social order. Amita Nijhawan is a Teaching Fellow in Dance at the University of Surrey. Among others she has published in Media/Culture Journal, South Asian Popular Culture, and PAJ. She is a kathak and yoga practitioner, and a creative writer.
After Dada: Fluxus as a Nomadic Art Movement
Authors: Wilmer Stephen
Published: January 2017

In this article Stephen Wilmer applies Deleuze and Guattari's concept of nomadology to the Fluxus art movement that spread across the world, breaking down barriers between art and life, privileging concrete and conceptual art, and staging unusual events. He traces Rosi Braidotti's development of Deleuze and Guattari's concept into her notion of the nomadic subject in which she favours factors such as geographic movement, transnational identities, common space (in accord with the Deleuzian differentiation between the divisible earth or private property, and nomadic space which belongs to everyone), polylingualism, desubjectivation, becoming minoritarian, and thinking and acting differently. With this as a philosophical and political context, the author investigates some of the artistic practices of specific Fluxus practitioners, especially the shamanistic performances and fat and felt installations of Joseph Beuys that supposedly owed their inspiration to his experience with nomadic Tatars. Stephen Wilmer is Professor Emeritus of Drama at Trinity College Dublin. He co-edited (with Audronė Žukauskaitė) Resisting Biopolitics: Philosophical, Political, and Performative Strategies (Routledge, 2016) and Deleuze and Beckett (Palgrave Macmillan, 2015). He edited ‘Theatre and the Nomadic Subject’ for Nordic Theatre Studies (2015), and co-edited (with Azadeh Sharifi) ‘Theatre and Statelessness in Europe’ for Critical Stages (2016).
Reduced competence of immature and mature oocytes vitrified by Cryotop method: assessment byin vitrofertilization and parthenogenetic activation in a bovine model
Authors: Bulgarelli Daiane L. , Vireque Alessandra A. , Pitangui-Molina Caroline P. , Silva-de-Sá Marcos F. , de Sá Rosa-e-Silva Ana Carolina J.
Published: January 2017

This study aimed to evaluate the embryo development competence, the nuclear maturation and the viability of germinal vesicle (GV) and metaphase II (MII) oocytes vitrified by the Cryotop method. Cumulus–oocyte complexes were derived from bovine ovaries and three experiments were conducted. In Experiment 1, GV oocytes were vitrified and underwentin vitromaturation (IVM) or not and their nuclear maturation was assessed by orcein staining. In Experiment 2, GV oocytes and MII oocytes were vitrified or not and the viability was assessed by calcein/ethidium homodimer-1 staining. In Experiment 3, MII oocytes matured before or after vitrification were submitted toin vitrofertilization (IVF) and parthenogenetic activation (PA) in order to evaluate embryo development. No difference was found for the nuclear maturation rate in the GV group (50%) and the GV control group (67%;P= 0.23) and for viability rate (56%; 77%;P= 0.055, respectively). However, in the MII group (27%) viability was significantly lower than that of the MII control group (84%;P< 0.0001). The cleavage rate by IVF and PA was similar in the GV group and the MII group. In contrast, vitrified MII oocytes showed no capacity for blastocyst development after IVF or PA and vitrified GV oocytes were able to develop to blastocysts only after PA, but not after IVF. In conclusion, oocyte vitrification by the Cryotop method reduced the capacity for embryo development. Vitrification of GV oocytes, however, did not influence the capacity of meiotic nuclear maturation and they exhibited higher viability following vitrification at the MII stage.
Prophylactic orthosteric inhibition of leukocyte integrin CD11b/CD18 prevents long-term fibrotic kidney failure in cynomolgus monkeys
Authors: Dehnadi Abbas , Benedict Cosimi A. , Neal Smith Rex , Li Xiangen , Alonso José L. , Means Terry K. , Arnaout M. Amin
Published: January 2017

Ischaemic acute kidney injury (AKI), an inflammatory disease process, often progresses to chronic kidney disease (CKD), with no available effective prophylaxis. This is in part due to lack of clinically relevant CKD models in non-human primates. Here we demonstrate that inhibition of the archetypal innate immune receptor CD11b/CD18 prevents progression of AKI to CKD in cynomolgus monkeys. Severe ischaemia-reperfusion injury of the right kidney, with subsequent periods of the left ureter ligation, causes irreversible right kidney failure 3, 6 or 9 months after AKI. Moreover, prophylactic inactivation of CD11b/CD18, using the orthosteric CD11b/CD18 inhibitor mAb107, improves microvascular perfusion and histopathology, reduces intrarenal pro-inflammatory mediators and salvages kidney function long term. These studies reveal an important early role of CD11b+ leukocytes in post-ischaemic kidney fibrosis and failure, and suggest a potential early therapeutic intervention to mitigate progression of ischaemic AKI to CKD in humans.
Mesoscopic superconductivity and high spin polarization coexisting at metallic point contacts on Weyl semimetal TaAs
Authors: Aggarwal Leena , Gayen Sirshendu , Das Shekhar , Kumar Ritesh , Süß Vicky , Felser Claudia , Shekhar Chandra , Sheet Goutam
Published: January 2017

A Weyl semimetal is a topologically non-trivial phase of matter that hosts mass-less Weyl fermions, the particles that remained elusive for more than 80 years since their theoretical discovery. The Weyl semimetals exhibit unique transport properties and remarkably high surface spin polarization. Here we show that a mesoscopic superconducting phase with critical temperature Tc=7 K can be realized by forming metallic point contacts with silver (Ag) on single crystals of TaAs, while neither Ag nor TaAs are superconductors. Andreev reflection spectroscopy of such point contacts reveals a superconducting gap of 1.2 meV that coexists with a high transport spin polarization of 60% indicating a highly spin-polarized supercurrent flowing through the point contacts on TaAs. Therefore, apart from the discovery of a novel mesoscopic superconducting phase, our results also show that the point contacts on Weyl semimetals are potentially important for applications in spintronics.
PhotoGate microscopy to track single molecules in crowded environments
Authors: Belyy Vladislav , Shih Sheng-Min , Bandaria Jigar , Huang Yongjian , Lawrence Rosalie E. , Zoncu Roberto , Yildiz Ahmet
Published: January 2017

Tracking single molecules inside cells reveals the dynamics of biological processes, including receptor trafficking, signalling and cargo transport. However, individual molecules often cannot be resolved inside cells due to their high density. Here we develop the PhotoGate technique that controls the number of fluorescent particles in a region of interest by repeatedly photobleaching its boundary. PhotoGate bypasses the requirement of photoactivation to track single particles at surface densities two orders of magnitude greater than the single-molecule detection limit. Using this method, we observe ligand-induced dimerization of a receptor tyrosine kinase at the cell surface and directly measure binding and dissociation of signalling molecules from early endosomes in a dense cytoplasm with single-molecule resolution. We additionally develop a numerical simulation suite for rapid quantitative optimization of Photogate experimental conditions. PhotoGate yields longer tracking times and more accurate measurements of complex stoichiometry than existing single-molecule imaging methods.
The local nature of incompressibility of quantum Hall effect
Authors: Kendirlik E. M. , Sirt S. , Kalkan S. B. , Ofek N. , Umansky V. , Siddiki A.
Published: January 2017

Since the experimental realization of the integer quantum Hall effect in a two-dimensional electron system, the interrelation between the conductance quantization and the topological properties of the system has been investigated. Assuming that the two-dimensional electron system is described by a Bloch Hamiltonian, system is insulating in the bulk of sample throughout the quantum Hall plateau due to a magnetic field induced energy gap. Meanwhile, the system is conducting at the edges resembling a 2+1 dimensional topological insulator without time-reversal symmetry. Here, by our magneto-transport measurements performed on GaAs/AlGaAs high purity Hall bars with two inner contacts we show that incompressible strips formed at the edges result in Hall quantization, even if the bulk is compressible. Consequently, the relationship between the quantum Hall effect and topological bulk insulator breaks for specific field intervals within the plateaus. The measurement of conducting bulk, strongly challenges all existing single-particle theories.
Improved ethanol electrooxidation performance by shortening Pd–Ni active site distance in Pd–Ni–P nanocatalysts
Authors: Chen Lin , Lu Lilin , Zhu Hengli , Chen Yueguang , Huang Yu , Li Yadong , Wang Leyu
Published: January 2017

Incorporating oxophilic metals into noble metal-based catalysts represents an emerging strategy to improve the catalytic performance of electrocatalysts in fuel cells. However, effects of the distance between the noble metal and oxophilic metal active sites on the catalytic performance have rarely been investigated. Herein, we report on ultrasmall (∼5 nm) Pd–Ni–P ternary nanoparticles for ethanol electrooxidation. The activity is improved up to 4.95 A per mgPd, which is 6.88 times higher than commercial Pd/C (0.72 A per mgPd), by shortening the distance between Pd and Ni active sites, achieved through shape transformation from Pd/Ni–P heterodimers into Pd–Ni–P nanoparticles and tuning the Ni/Pd atomic ratio to 1:1. Density functional theory calculations reveal that the improved activity and stability stems from the promoted production of free OH radicals (on Ni active sites) which facilitate the oxidative removal of carbonaceous poison and combination with CH3CO radicals on adjacent Pd active sites.
Parkinsonian motor impairment predicts personality domains related to genetic risk and treatment outcomes in schizophrenia
Authors: Molina Juan L , Calvó María , Padilla Eduardo , Balda Mara , Alemán Gabriela González , Florenzano Néstor V , Guerrero Gonzalo , Kamis Danielle , Rangeon Beatriz Molina , Bourdieu Mercedes , Strejilevich Sergio A , Conesa Horacio A , Escobar Javier I , Zwir Igor , Cloninger C Robert , de Erausquin Gabriel A
Published: January 2017

Identifying endophenotypes of schizophrenia is of critical importance and has profound implications on clinical practice. Here we propose an innovative approach to clarify the mechanims through which temperament and character deviance relates to risk for schizophrenia and predict long-term treatment outcomes. We recruited 61 antipsychotic naïve subjects with chronic schizophrenia, 99 unaffected relatives, and 68 healthy controls from rural communities in the Central Andes. Diagnosis was ascertained with the Schedules of Clinical Assessment in Neuropsychiatry; parkinsonian motor impairment was measured with the Unified Parkinson’s Disease Rating Scale; mesencephalic parenchyma was evaluated with transcranial ultrasound; and personality traits were assessed using the Temperament and Character Inventory. Ten-year outcome data was available for ~40% of the index cases. Patients with schizophrenia had higher harm avoidance and self-transcendence (ST), and lower reward dependence (RD), cooperativeness (CO), and self-directedness (SD). Unaffected relatives had higher ST and lower CO and SD. Parkinsonism reliably predicted RD, CO, and SD after correcting for age and sex. The average duration of untreated psychosis (DUP) was over 5 years. Further, SD was anticorrelated with DUP and antipsychotic dosing at follow-up. Baseline DUP was related to antipsychotic dose-years. Further, ‘explosive/borderline’, ‘methodical/obsessive’, and ‘disorganized/schizotypal’ personality profiles were associated with increased risk of schizophrenia. Parkinsonism predicts core personality features and treatment outcomes in schizophrenia. Our study suggests that RD, CO, and SD are endophenotypes of the disease that may, in part, be mediated by dopaminergic function. Further, SD is an important determinant of treatment course and outcome.
Origin and evolution of MIR1444 genes in Salicaceae
Authors: Wang Meizhen , Li Caili , Lu Shanfa
Published: January 2017

miR1444s are functionally significant miRNAs targeting polyphenol oxidase (PPO) genes for cleavage. MIR1444 genes were reported only in Populus trichocarpa. Through the computational analysis of 215 RNA-seq data, four whole genome sequences of Salicaceae species and deep sequencing of six P. trichocarpa small RNA libraries, we investigated the origin and evolution history of MIR1444s. A total of 23 MIR1444s were identified. Populus and Idesia species contain two MIR1444 genes, while Salix includes only one. Populus and Idesia MIR1444b genes and Salix MIR1444s were phylogenetically separated from Populus and Idesia MIR1444a genes. Ptr-miR1444a and ptr-miR1444b showed sequence divergence. Compared with ptr-miR1444b, ptr-miR1444a started 2 nt upstream of precursor, resulting in differential regulation of PPO targets. Sequence alignments showed that MIR1444 genes exhibited extensive similarity to their PPO targets, the characteristics of MIRs originated from targets through an inverted gene duplication event. Genome sequence comparison showed that MIR1444 genes in Populus and Idesia were expanded through the Salicoid genome duplication event. A copy of MIR1444 gene was lost in Salix through DNA segment deletion during chromosome rearrangements. The results provide significant information for the origin of plant miRNAs and the mechanism of Salicaceae gene evolution and divergence.
Self-Assembly Assisted Fabrication of Dextran-Based Nanohydrogels with Reduction-Cleavable Junctions for Applications as Efficient Drug Delivery Systems
Authors: Wang Hao , Dai Tingting , Zhou Shuyan , Huang Xiaoxiao , Li Songying , Sun Kang , Zhou Guangdong , Dou Hongjing
Published: January 2017

In order to overcome the key challenge in improving both fabrication efficiency and their drug delivery capability of anti-cancer drug delivery systems (ACDDS), here polyacrylic acid (PAA) grafted dextran (Dex) nanohydrogels (NGs) with covalent crosslinked structure bearing redox sensitive disulfide crosslinking junctions (Dex-SS-PAA) were synthesized efficiently through a one-step self-assembly assisted methodology (SAA). The Dex-SS-PAA were subsequently conjugated with doxorubicin through an acid-labile hydrazone bond (Dex-SS-PAA-DOX). The in vitro drug release behavior, anti-cancer effects in vivo, and biosafety of the as-prepared acid- and redox-dual responsive biodegradable NGs were systematically investigated. The results revealed that the Dex-SS-PAA-DOX exhibited pH- and redox-controlled drug release, greatly reduced the toxicity of free DOX, while exhibiting a strong ability to inhibit the growth of MDA-MB-231 tumors. Our study demonstrated that the Dex-SS-PAA-DOX NGs are very promising candidates as ACDDS for anti-cancer therapeutics.
Epileptiform activity in the mouse visual cortex interferes with cortical processing in connected areas
Authors: Petrucco L. , Pracucci E. , Brondi M. , Ratto G. M. , Landi S.
Published: January 2017

Epileptiform activity is associated with impairment of brain function even in absence of seizures, as demonstrated by failures in various testing paradigm in presence of hypersynchronous interictal spikes (ISs). Clinical evidence suggests that cognitive deficits might be directly caused by the anomalous activity rather than by its underlying etiology. Indeed, we seek to understand whether ISs interfere with neuronal processing in connected areas not directly participating in the hypersynchronous activity in an acute model of epilepsy. Here we cause focal ISs in the visual cortex of anesthetized mice and we determine that, even if ISs do not invade the opposite hemisphere, the local field potential is subtly disrupted with a modulation of firing probability imposed by the contralateral IS activity. Finally, we find that visual processing is altered depending on the temporal relationship between ISs and stimulus presentation. We conclude that focal ISs interact with normal cortical dynamics far from the epileptic focus, disrupting endogenous oscillatory rhythms and affecting information processing.
Structures, stabilities and spectral properties of borospherene B44− and metalloborospherenes MB440/− (M = Li, Na, and K)
Authors: Li Shixiong , Zhang Zhengping , Long Zhengwen , Qin Shuijie
Published: January 2017

Density functional theory (DFT) and time-dependent density functional theory (TD-DFT) calculations are carried out to study the stabilities, photoelectron, infrared, Raman and electronic absorption spectra of borospherene B44− and metalloborospherenes MB440/− (M = Li, Na, and K). It is found that all atoms can form stable exohedral metalloborospherenes M&B440/−, whereas only Na and K atoms can be stably encapsulated inside B440/− cage. In addition, relative energies of these metalloborospherenes suggest that Na and K atoms favor exohedral configuration. Importantly, doping of metal atom can modify the stabilities of B44 with different structures, which provides a possible route to produce stable boron clusters or metalloborospherenes. The calculated results suggest that B44 tends to get electrons from the doped metal. Metalloborospherenes MB44− are characterized as charge-transfer complexes (M2+B442−), where B44 tends to get two electrons from the extra electron and the doped metal, resulting in similar features with anionic B442−. In addition, doping of metal atom can change the spectral features, such as blueshift or redshift and weakening or strengthening of characteristic peaks, since the extra metal atom can modify the electronic structure. The calculated spectra are readily compared with future spectroscopy measurements and can be used as fingerprints to identify B44− and metalloborospherenes.
Ion irradiation induced structural modifications and increase in elastic modulus of silica based thin films
Authors: Shojaee S. A. , Qi Y. , Wang Y. Q. , Mehner A. , Lucca D. A.
Published: January 2017

Ion irradiation is an alternative to heat treatment for transforming organic-inorganic thin films to a ceramic state. One major shortcoming in previous studies of ion-irradiated films is the assumption that constituent phases in ion-irradiated and heat-treated films are identical and that the ion irradiation effect is limited to changes in composition. In this study, we investigate the effects of ion irradiation on both the composition and structure of constituent phases and use the results to explain the measured elastic modulus of the films. The results indicated that the microstructure of the irradiated films consisted of carbon clusters within a silica matrix. It was found that carbon was present in a non-graphitic sp2-bonded configuration. It was also observed that ion irradiation caused a decrease in the Si-O-Si bond angle of silica, similar to the effects of applied pressure. A phase transformation from tetrahedrally bonded to octahedrally bonded silica was also observed. The results indicated the incorporation of carbon within the silica network. A combination of the decrease in Si-O-Si bond angle and an increase in the carbon incorporation within the silica network was found to be responsible for the increase in the elastic modulus of the films.
Diversity, distribution, and significance of transposable elements in the genome of the only selfing hermaphroditic vertebrate Kryptolebias marmoratus
Authors: Rhee Jae-Sung , Choi Beom-Soon , Kim Jaebum , Kim Bo-Mi , Lee Young-Mi , Kim Il-Chan , Kanamori Akira , Choi Ik-Young , Schartl Manfred , Lee Jae-Seong
Published: January 2017

The Kryptolebias marmoratus is unique because it is the only self-fertilizing hermaphroditic vertebrate, known to date. It primarily reproduces by internal self-fertilization in a mixed ovary/testis gonad. Here, we report on a high-quality genome assembly for the K. marmoratus South Korea (SK) strain highlighting the diversity and distribution of transposable elements (TEs). We find that K. marmoratus genome maintains number and composition of TEs. This can be an important genomic attribute promoting genome recombination in this selfing fish, while, in addition to a mixed mating strategy, it may also represent a mechanism contributing to the evolutionary adaptation to ecological pressure of the species. Future work should help clarify this point further once genomic information is gathered for other taxa of the family Rivulidae that do not self-fertilize. We provide a valuable genome resource that highlights the potential impact of TEs on the genome evolution of a fish species with an uncommon life cycle.
Plasma Amino Acid Profile in Patients with Aortic Dissection
Authors: Wang Linlin , Liu Sha , Yang Wengang , Yu Haitao , Zhang Li , Ma Ping , Wu Peng , Li Xue , Cho Kenka , Xue Song , Jiang Baohong
Published: January 2017

Aortic dissection (AD), a severe cardiovascular disease with the characteristics of high mortality, is lack of specific clinical biomarkers. In order to facilitate the diagnosis of AD, we investigated plasma amino acid profile through metabolomics approach. Total 33 human subjects were enrolled in the study: 11 coronary heart disease (CHD) patients without aortic lesion and 11 acute AD and 11 chronic AD. Amino acids were identified in plasma using liquid chromatography and mass spectrometry (LC-MS/MS), and were further subjected to multiple logistic regression analysis. The score plots of principal component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA) showed clear discrimination of CHD patients with AD, acute AD or chronic AD patients, respectively. The contents of histidine, glycine, serine, citrate, ornithine, hydroxyproline, proline and sarcosine were significant different in acute AD patients comparing with CHD patients. The levels of citrate, GABA, glutamate and cysteine were significant different in chronic AD patients comparing with CHD patients. The contents of glutamate and phenylalanine were significant changed in acute AD patients comparing with chronic AD patients. Plasma aminograms were significantly altered in patients with AD comparing with CHD, especially in acute AD, suggesting amino acid profile is expected to exploit a novel, non-invasive, objective diagnosis for AD.
Elucidating the modes of action for bioactive compounds in a cell-specific manner by large-scale chemically-induced transcriptomics
Authors: Iwata Michio , Sawada Ryusuke , Iwata Hiroaki , Kotera Masaaki , Yamanishi Yoshihiro
Published: January 2017

The identification of the modes of action of bioactive compounds is a major challenge in chemical systems biology of diseases. Genome-wide expression profiling of transcriptional responses to compound treatment for human cell lines is a promising unbiased approach for the mode-of-action analysis. Here we developed a novel approach to elucidate the modes of action of bioactive compounds in a cell-specific manner using large-scale chemically-induced transcriptome data acquired from the Library of Integrated Network-based Cellular Signatures (LINCS), and analyzed 16,268 compounds and 68 human cell lines. First, we performed pathway enrichment analyses of regulated genes to reveal active pathways among 163 biological pathways. Next, we explored potential target proteins (including primary targets and off-targets) with cell-specific transcriptional similarity using chemical–protein interactome. Finally, we predicted new therapeutic indications for 461 diseases based on the target proteins. We showed the usefulness of the proposed approach in terms of prediction coverage, interpretation, and large-scale applicability, and validated the new prediction results experimentally by anin vitrocellular assay. The approach has a high potential for advancing drug discovery and repositioning.
Nitrogen loss by anaerobic ammonium oxidation in unconfined aquifer soils
Authors: Wang Shanyun , Radny Dirk , Huang Shuangbing , Zhuang Linjie , Zhao Siyan , Berg Michael , Jetten Mike S. M. , Zhu Guibing
Published: January 2017

Anaerobic ammonium oxidation (anammox) is recognized as an important process for nitrogen cycling, yet little is known about its role in the subsurface biosphere. In this study, we investigated the presence, abundance, and role of anammox bacteria in upland soil cores from Tianjin, China (20 m depth) and Basel, Switzerland (10 m depth), using isotope-tracing techniques, (q)PCR assays, and 16 S rRNA & hzsB gene clone libraries, along with nutrient profiles of soil core samples. Anammox in the phreatic (water-saturated) zone contributed to 37.5–67.6% of the N-loss (up to 0.675 gN m−2d−1), with anammox activities of 0.005–0.74 nmolN g−1soil h−1, which were even higher than the denitrification rates. By contrast, no significant anammox was measured in the vadose zone. Higher anammox bacterial cell densities were observed (0.75–1.4 × 107copies g−1soil) in the phreatic zone, where ammonia-oxidizing bacteria (AOB) maybe the major source of nitrite for anammox bacteria. The anammox bacterial cells in soils of the vadose zone were all <103copies g−1soil. We suggest that the subsurface provides a favorable niche for anammox bacteria whose contribution to N cycling and groundwater nitrate removal seems considerably larger than previously known.
A comparative analysis of three vector-borne diseases across Australia using seasonal and meteorological models
Authors: Stratton Margaret D. , Ehrlich Hanna Y. , Mor Siobhan M. , Naumova Elena N.
Published: January 2017

Ross River virus (RRV), Barmah Forest virus (BFV), and dengue are three common mosquito-borne diseases in Australia that display notable seasonal patterns. Although all three diseases have been modeled on localized scales, no previous study has used harmonic models to compare seasonality of mosquito-borne diseases on a continent-wide scale. We fit Poisson harmonic regression models to surveillance data on RRV, BFV, and dengue (from 1993, 1995 and 1991, respectively, through 2015) incorporating seasonal, trend, and climate (temperature and rainfall) parameters. The models captured an average of 50–65% variability of the data. Disease incidence for all three diseases generally peaked in January or February, but peak timing was most variable for dengue. The most significant predictor parameters were trend and inter-annual periodicity for BFV, intra-annual periodicity for RRV, and trend for dengue. We found that a Temperature Suitability Index (TSI), designed to reclassify climate data relative to optimal conditions for vector establishment, could be applied to this context. Finally, we extrapolated our models to estimate the impact of a false-positive BFV epidemic in 2013. Creating these models and comparing variations in periodicities may provide insight into historical outbreaks as well as future patterns of mosquito-borne diseases.
New insights into the GINS complex explain the controversy between existing structural models
Authors: Carroni Marta , De March Matteo , Medagli Barbara , Krastanova Ivet , Taylor Ian A. , Amenitsch Heinz , Araki Hiroyuchi , Pisani Francesca M. , Patwardhan Ardan , Onesti Silvia
Published: January 2017

GINS is a key component of eukaryotic replicative forks and is composed of four subunits (Sld5, Psf1, Psf2, Psf3). To explain the discrepancy between structural data from crystallography and electron microscopy (EM), we show that GINS is a compact tetramer in solution as observed in crystal structures, but also forms a double-tetrameric population, detectable by EM. This may represent an intermediate step towards the assembly of two replicative helicase complexes at origins, moving in opposite directions within the replication bubble. Reconstruction of the double-tetrameric form, combined with small-angle X-ray scattering data, allows the localisation of the B domain of the Psf1 subunit in the free GINS complex, which was not visible in previous studies and is essential for the formation of a functional replication fork.
HCN1 channels reduce the rate of exocytosis from a subset of cortical synaptic terminals
Authors: Huang Zhuo , Li Gengyu , Aguado Carolina , Lujan Rafael , Shah Mala M.
Published: January 2017

The hyperpolarization-activated cyclic nucleotide-gated (HCN1) channels are predominantly located in pyramidal cell dendrites within the cortex. Recent evidence suggests these channels also exist pre-synaptically in a subset of synaptic terminals within the mature entorhinal cortex (EC). Inhibition of pre-synaptic HCN channels enhances miniature excitatory post-synaptic currents (mEPSCs) onto EC layer III pyramidal neurons, suggesting that these channels decrease the release of the neurotransmitter, glutamate. Thus, do pre-synaptic HCN channels alter the rate of synaptic vesicle exocytosis and thereby enhance neurotransmitter release? To address this, we imaged the release of FM1-43, a dye that is incorporated into synaptic vesicles, from EC synaptic terminals using two photon microscopy in slices obtained from forebrain specific HCN1 deficient mice, global HCN1 knockouts and their wildtype littermates. This coupled with electrophysiology and pharmacology showed that HCN1 channels restrict the rate of exocytosis from a subset of cortical synaptic terminals within the EC and in this way, constrain non-action potential-dependent and action potential-dependent spontaneous release as well as synchronous, evoked release. Since HCN1 channels also affect post-synaptic potential kinetics and integration, our results indicate that there are diverse ways by which HCN1 channels influence synaptic strength and plasticity.
Increased levels of CSF total but not oligomeric or phosphorylated forms of alpha-synuclein in patients diagnosed with probable Alzheimer’s disease
Authors: Majbour Nour K. , Chiasserini Davide , Vaikath Nishant N. , Eusebi Paolo , Tokuda Takahiko , van de Berg Wilma , Parnetti Lucilla , Calabresi Paolo , El-Agnaf Omar M. A.
Published: January 2017

Several studies reported an association between CSF alpha-synuclein (α-syn) and tau in Alzheimer’s disease (AD), and demonstrated the significance of α-syn in improving the diagnostic sensitivity/specificity of classical AD CSF biomarkers. In the current study, we measured CSF levels of different α-syn species in a cohort of AD patients (n = 225) who showed a CSF profile typical of AD at baseline as well as in cognitively intact controls (n = 68). CSF total α-syn (t-α-syn) significantly increased in the AD group (p < 0.0001) compared to controls, while oligomeric- and phosphorylated-Ser129-α-syn did not change significantly. ROC analysis showed a sensitivity of 85% and a specificity of 84% (AUC = 0.88) in distinguishing AD from controls. T-α-syn levels correlated positively with tau species in AD group and negatively with baseline MMSE score. Our data support the added value of measurement of CSF α-syn species for further characterization of the CSF AD profile.
Haploinsufficiency of EHMT1 improves pattern separation and increases hippocampal cell proliferation
Authors: Benevento Marco , Oomen Charlotte A. , Horner Alexa E. , Amiri Houshang , Jacobs Tessa , Pauwels Charlotte , Frega Monica , Kleefstra Tjitske , Kopanitsa Maksym V. , Grant Seth G. N. , Bussey Timothy J. , Saksida Lisa M. , Van der Zee Catharina E.E.M. , van Bokhoven Hans , Glennon Jeffrey C. , Kasri Nael Nadif
Published: January 2017

Heterozygous mutations or deletions of the human Euchromatin Histone Methyltransferase 1 (EHMT1) gene are the main causes of Kleefstra syndrome, a neurodevelopmental disorder that is characterized by impaired memory, autistic features and mostly severe intellectual disability. Previously, Ehmt1+/− heterozygous knockout mice were found to exhibit cranial abnormalities and decreased sociability, phenotypes similar to those observed in Kleefstra syndrome patients. In addition, Ehmt1+/− knockout mice were impaired at fear extinction and novel- and spatial object recognition. In this study, Ehmt1+/− and wild-type mice were tested on several cognitive tests in a touchscreen-equipped operant chamber to further investigate the nature of learning and memory changes. Performance of Ehmt1+/− mice in the Visual Discrimination & Reversal learning, object-location Paired-Associates learning- and Extinction learning tasks was found to be unimpaired. Remarkably, Ehmt1+/− mice showed enhanced performance on the Location Discrimination test of pattern separation. In line with improved Location Discrimination ability, an increase in BrdU-labelled cells in the subgranular zone of the dentate gyrus was observed. In conclusion, reduced levels of EHMT1 protein in Ehmt1+/− mice does not result in general learning deficits in a touchscreen-based battery, but leads to increased adult cell proliferation in the hippocampus and enhanced pattern separation ability.