bluuebunny/crossref_metadata_2025 huggingface dataset:
Intra‐tumor heterogeneity in head and neck cancer and its clinical implications
Authors: Mroz Edmund A. , Rocco James W.
Published: July 2016

The presence of heritable differences among cancer cells within a tumor, called intra‐tumor genetic heterogeneity, has long been suspected of playing a role in poor responses to therapy. Research over the past decade has documented the existence of such heterogeneity within tumors of individual patients and documented its potential clinical significance. The research methods for identifying this heterogeneity were not, however, readily adaptable to widespread clinical application. After a brief review of this background, we describe the development of a measure of intra‐tumor genetic heterogeneity, based on whole‐exome sequencing of individual tumor samples, that could be applied to biopsy specimens in a clinical setting. This measure has now been used in head and neck squamous cell carcinoma (HNSCC) to document, for the first time, a relation of high intra‐tumor genetic heterogeneity to shorter overall survival in a large, multi‐institutional study. The implications of heterogeneity for research and clinical care thus now need to be addressed.
Current State of Antimicrobial Stewardship at Solid Organ and Hematopoietic Cell Transplant Centers in the United States
Authors: Seo Susan K. , Lo Kaming , Abbo Lilian M.
Published: July 2016

OBJECTIVE

To assess the extent of antimicrobial stewardship programs (ASPs) at solid organ transplant (SOT) and hematopoietic cell transplant (HCT) centers in the United States.

DESIGN

An 18-item voluntary survey was developed to gauge current antimicrobial stewardship practices in transplant patients, examine the availability and perceived usefulness of novel diagnostics and azole levels to guide therapy, and identify challenges for implementation of ASPs at these centers.

PARTICIPANTS

The survey was distributed electronically to infectious disease physicians and pharmacists at adult and pediatric SOT and HCT centers during May 1–22, 2015. Facilities were deidentified.

RESULTS

After duplicate removal, 71 (56%) of 127 unique transplant centers in 32 states were analyzed. Forty-four sites (62%) performed at least 100 SOT annually, and 40 (56%) performed at least 100 HCT annually. Top 5 stewardship activities encompassing transplant patients were formulary restriction, guideline development, prospective audit and feedback, education, and dose optimization. Respiratory viral panels (66/66 [100%]), azole levels (64/66 [97%]), and serum/bronchoalveolar lavage galactomannan (58/66 [88%]) were perceived as most useful to guide therapy. Apparent challenges to antimicrobial stewardship included undefined duration for certain infections (53/59 [90%]), diagnostic uncertainty (47/59 [80%]), the perception that antibiotic-resistant infections required escalation (42/59 [71%]), prescriber opposition (41/59 [69%]), and costly drugs (37/59 [63%]).

CONCLUSIONS

ASP activities were performed at many adult and pediatric SOT and HCT centers in the United States. Diagnostic and therapeutic uncertainty in transplant patients is challenging for ASPs. Collaborative research should examine the impact of antimicrobial stewardship practices in SOT and HCT.

Infect Control Hosp Epidemiol2016;1–6
Morphological and molecular analyses of a new species of Saccocoelioides Szidat, 1954 (Haploporidae Nicoll, 1914) in the fat sleeper Dormitator maculatus (Bloch) (Perciformes: Eleotridae) from the Gulf of Mexico
Authors: Andrade-Gómez L. , Pinacho-Pinacho C.D. , Hernández-Orts J.S. , Sereno-Uribe A.L. , García-Varela M.
Published: July 2016

Saccocoelioides olmecae n. sp. is described from specimens recovered from the intestine of the fat sleeper Dormitator maculatus (Bloch) (Perciformes: Eleotridae) collected in six localities along the coast of the Gulf of Mexico. The new species is mainly distinguished from the other three described species of Saccocoelioides Szidat, 1954 from North and Middle America (i.e. S. sogandaresi Lumsden, 1963, S. chauhani Lamothe-Argumedo, 1974 and S. lamothei Aguirre-Macedo & Violante-González, 2008) by having an elongated body, a sac-like caecum, a uterus that extends to the first third of body and by having vitelline follicles longitudinally elongated reaching the posterior end of the body. Sequences of the large subunit (LSU) of the ribosomal DNA, including the domain D1–D3, and the internal transcribed spacer 2 (ITS2) were used independently and concatenated to corroborate the morphological distinction among S. olmecae n. sp., S. chauhani and S. lamothei from freshwater and brackish-water fish from Middle America. The genetic divergence estimated among the three species of Saccocoelioides was very low: 1% for LSU and from 1 to 4% for ITS2. Maximum likelihood and Bayesian inference analyses for each dataset and both datasets combined revealed that S. olmecae n. sp. represents an independent clade with moderate bootstrap support and posterior probabilities. This is the third species of Saccocoelioides described in Mexico, and the 17th species from the Americas.
Flops
Authors: Kollár János
Published: July 2016

The aim of this note is to study birational transformations of three-folds with nef canonical classes. One would like to write any such map as a composite of certain simple and basic transformations.

A special case was first considered by Kulikov [Ku] and later extensively studied by several authors. The next main conceptual step was Reid’s study [R2] of small resolutions of terminal threefold singularities. He obtained the elementary birational transformations as follows: find a copy of such a small resolution inside the threefold and then replace it with another resolution. This approach was extended by Kawamata [K3] to canonical singularities.
Discrete Schrödinger operators on a graph
Authors: Wee Sy Polly , Sunada Toshikazu
Published: July 2016

In this paper, we study some spectral properties of the discrete Schrödinger operator = Δ + q defined on a locally finite connected graph with an automorphism group whose orbit space is a finite graph.

The discrete Laplacian and its generalization have been explored from many different viewpoints (for instance, see [2] [4]). Our paper discusses the discrete analogue of the results on the bottom of the spectrum established by T. Kobayashi, K. Ono and T. Sunada [3] in the Riemannian-manifold-setting.
Cofiniteness of local cohomology modules for ideals of dimension one
Authors: Yoshida Ken-Ichi
Published: July 2016

In this paper, we prove that for any ideal I of dimension one is I-cofinite for all i and for any finite A-module M. Furthermore, for any ideal I over any regular local ring A, we investigate the relationship between I-cofiniteness and vanishing for local cohomology modules .
A Characterization of Invariant Affine Connections
Authors: Kostant Bertram
Published: July 2016

1. Introduction and statement of theorem. 1. In [1] Ambrose and Singer gave a necessary and sufficient condition (Theorem 3 here) for a simply connected complete Riemannian manifold to admit a transitive group of motions. Here we shall give a simple proof of a more general theorem — Theorem 1 (the proof of Theorem 1 became suggestive to us after we noted that the Tx of [1] is just the ax of [6] when X is restricted to p0, see [6], p. 539).
The structure of pointwise recurrent maps having the pseudo orbit tracing property
Authors: Mai Jiehua , Ye Xiangdong
Published: July 2016

We show that a continuous map of a metric space is pointwise recurrent and has the pseudo orbit tracing property if and only if the map is uniformly conjugate to an adding-machine-like map restricted to some invariant subset.
Coxeter Orbits and Modular Representations
Authors: Bonnafé Cédric , Rouquier Raphaël
Published: July 2016

We study the modular representations of finite groups of Lie type arising in the cohomology of certain quotients of Deligne-Lusztig varieties associated with Coxeter elements. These quotients are related to Gelfand-Graev representations and we present a conjecture on the Deligne-Lusztig restriction of Gelfand-Graev representations. We prove the conjecture for restriction to a Coxeter torus. We deduce a proof of Brouée’s conjecture on equivalences of derived categories arising from Deligne-Lusztig varieties, for a split group of type An and a Coxeter element. Our study is based on Lusztig’s work in characteristic 0 [Lu2].
The Absolute Galois Group of the Field of Totally S-Adic Numbers
Authors: Haran Dan , Jarden Moshe , Pop Florian
Published: July 2016

For a finite set S of primes of a number field K and for σ1,…, σe ∈ Gal(K) we denote the field of totally S-adic numbers by Ktot,S and the fixed field of σ1,…,σe in Ktot,S by Ktot,S(σ). We prove that foralmost all σ ∈ Gal(K)e the absolute Galois group of Ktot,S(σ) is the free product of and a free product of local factors over S.
Some remarks concerning Demazure’s construction of normal graded rings
Authors: Watanabe Keiichi
Published: July 2016

In [1], Demazure showed a new way of constructing normal graded rings using the concept of “rational coefficient Weil divisors” of normal projective varieties and he showed, among other things, the following

THEOREM ([1], 3.5). If R = ⊕n ≥ 0Rn is a normal graded ring of finite type over a field k and if T is a homogeneous element of degree 1 in the quotient field of R, then there exists unique divisor D ∈ Div (X, Q) (X = Proj (R)), such that for every n ≧ 0.(See (1.1) for the definition of
On non-local problems for parabolic equations
Authors: Chabrowski J.
Published: July 2016

The main purposes of this paper are to investigate the existence and the uniqueness of a non-local problem for a linear parabolic equation

in a cylinder D = Ω × (0, T].
Almost paracontact and parahodge structures on manifolds
Authors: Kaneyuki Soji , Williams Floyd L.
Published: July 2016

In this paper we study the paracomplex analogues of almost contact structures, and we introduce and study the notion of parahodge structures on manifolds. In particular, we construct new examples of paracomplex manifolds and we find all simply connected parahermitian symmetric coset spaces, which are the adjoint orbits of noncompact simple Lie groups, with parahodge structures induced by the Killing forms. This is done by (i) observing that a version of the results of A. Morimoto [4] on almost contact structures can be formulated and proved for almost paracontact structures, and by (ii) the methods of geometric quantization [3] applied to parahermitian symmetric triples [1] in conjunction with results of [7]. Two of the main results are Theorem 2.5 (which ties together the above structures) and Corollary 3.9.
A Theorem on the Affine Transformation Group of a Riemannian Manifold
Authors: Kobayashi Shoshichi
Published: July 2016

Every Riemannian manifold has a unique affine connection without torsion, which is necessarily invariant by any isometrical transformation of the manifold. However, an affine transformation (i.e., transformation leaving invariant the affine connection) is not necessarily an isometrical transformation. (Consider, for example, the ordinary Euclidean space).
Über eine zur Frattini-Gruppe duale Bildung
Authors: Itô Noboru
Published: July 2016

Es ist wohlbekannt, dass die Frattini-Gruppe einer endlichen Gruppe G, mit anderen Worten, der Durchschnitt aller maximalen Untergruppen von G, nilpotent ist. Offen ist dagegen bis jetzt die Frage, ob die Faktorgruppe G/F*(G) von G nach dem Erzeugnis F*(G) aller minimalen Untergruppen eine besondere Struktur besitzt, z. B. ob sie auflösbar ist. Mehrere Schwierigkeiten sind der Grund hierfür: Einmal ist G/F*(G) im allgemeinen nicht nilpotent, zum anderen kennen wir die Struktur der einfachen und auflösbaren Gruppen (abgesehen von der Theorie von P. Hall) zu wenig. In der vorliegenden Note sollen teilweise Antworten auf die Frage nach der Auflösbarkeit von G/F*(G) gegeben werden.
Fixed Points of Isometries
Authors: Kobayashi Shoshichi
Published: July 2016

The purpose of this paper is to prove the following

Theorem. Let M be a Riemannian manifold of dimension n and let ξ be a Killing vector field (i.e., infinitesimal isometry) of M. Let F be the set of points x of M where ξ vanishes and let F = ∪ Vi, where the Vi’s are the connected components of F. Then (assuming F to be non-empty)
Hodge structure on twisted cohomologies and twisted Riemann inequalities I
Authors: Hanamura Masaki , Yoshida Masaaki
Published: July 2016

We show the twisted cohomology onhas a natural polarized Hodge structure and hence derive the analogues of Riemann’s equality and inequailty.
Some estimates for the Bergman Kernel and Metric in Terms of Logarithmic Capacity
Authors: Błocki Zbigniew
Published: July 2016

For a bounded domain Ω on the plane we show the inequality cΩ(z)2 ≤ 2πKΩ(z), z ∈ Ω, where cΩ(z) is the logarithmic capacity of the complement ℂ\Ω with respect to z and KΩ is the Bergman kernel. We thus improve a constant in an estimate due to T. Ohsawa but fall short of the inequality cΩ(z)2 ≤ πKΩ(z) conjectured by N. Suita. The main tool we use is a comparison, due to B. Berndtsson, of the kernels for the weighted complex Laplacian and the Green function. We also show a similar estimate for the Bergman metric and analogous results in several variables.
Skin conductance and schizophrenic symptomatology
Authors: Campo J. à , Merckelbach H.L.G.J. , Nijman H. , Yeates-Frederikx M. , Allertz W.
Published: July 2016

Skin conductance is a psychophysiological parameter that reflects fundamental processes such as attention and arousal. The present study explored whether deviations in skin conductance activity are associated with severity of schizophrenic symptoms. For this purpose, Skin Conductance Responses (SCRs) to discrete stimuli (80 dB noises) and Skin Conductance Levels (SCLs) of 37 schizophrenic patients and 31 healthy volunteers were recorded. In accordance with previous studies, schizophrenic patients were found to be hyporesponsive compared to healthy controls. More specifically, almost half of the patients (46%) did not react with any SCR to the first 3 stimuli, whereas only 10% of the control group exhibited such a non-responding. Accordingly, the mean amplitude of the first 3 SCRs – as measured in u Siemens – was found to be significantly lower in patients compared to controls. As well, mean SCL was found to be (marginally) elevated in the patient group. This was especially the case for patients who did exhibit SCRs. In the patient group, a negative correlation was found between amplitude of SCRs and symptom severity. This association was mainly carried by a significant correlation between positive symptoms and reduced SCRs. The clinical relevance of these findings is discussed in detail.
Serum prolactin levels and sexual dysfunctions in antipsychotic medication, such as risperidone: a review
Authors: Knegtering H. , Lambers P.A. , Prakken G. , ten Brink C.
Published: July 2016

Classical antipsychotic drugs increase the level of serum prolactin. The atypical antipsychotic clozapine barely increases prolactin levels. An open naturalistic study in the University Hospital of Groningen suggests that treatment with risperidone in comparison to classical antipsychotics seems to increase the risk of erectile and ejaculatory disorders in male patients and to menstrual disturbances in female patients. In the literature reviewed, risperidone is associated with higher prolactin levels in comparison to classical antipsychotics. It is still unclear which mechanism is responsible for the increase of serum prolactin levels and sexual dysfunctions in patients using risperidone. Dopaminergic and serotonergic receptor blockade seems to play an important role. Other mechanisms are discussed.
Schizophrenia among patients with systemic lupus erythematosus: population-based cross-sectional study
Authors: Tiosano S. , Farhi A. , Watad A. , Grysman N. , Stryjer R. , Amital H. , Comaneshter D. , Cohen A. D. , Amital D.
Published: July 2016

Aims.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease involving multiple organs, including the central nervous system. Evidence of immune dysfunction exists also in schizophrenia, a psychiatric illness involving chronic or recurrent psychosis. The aim of our study was to investigate if there is an epidemiological association between SLE and schizophrenia.

Method.

A cross-sectional study was conducted comparing patients with SLE with age and gender-matched controls regarding the proportion of patients with comorbid schizophrenia. χ2- and t-tests were used for univariate analysis, and interaction of schizophrenia with SLE across strata of covariates was checked. A logistic regression model was used for multivariate analysis. The study was performed utilising the medical database of Clalit Health Services in Israel.

Results.

The study included 5018 patients with SLE and 25 090 controls. SLE patients had a female predominance, and a higher proportion of smoking compared with age and sex-matched controls. In multivariate analysis, SLE was found to be independently associated with schizophrenia while controlling for age, gender, socioeconomic status (SES) and smoking (OR 1.33, p = 0.042).

Conclusions.

We found a positive association between SLE and schizophrenia across patients of different age, gender and SES. This association can contribute to understanding the pathophysiology of the two disorders and may also have clinical implications for earlier as well as better diagnosis and treatment.
Revising the Displacement History of New Zealand's Alpine Fault
Authors: Cook Terri
Published: July 2016

A reinterpretation of structural and paleomagnetic data suggests that New Zealand's Alpine Fault accommodates a far greater percentage of geologically recent plate motion than previously thought.
USGS Seeks to Contain Damage from Scientific Misconduct at Lab
Authors: Showstack Randy
Published: July 2016

Although damage from the specific incident "is relatively well contained," the issue threatens the agency's reputation for high-quality science and goes counter to its standards, according to a USGS official.
The antibiotic resistome of swine manure is significantly altered by association with the Musca domestica larvae gut microbiome
Authors: Wang Hang , Sangwan Naseer , Li Hong-Yi , Su Jian-Qiang , Oyang Wei-Yin , Zhang Zhi-Jian , Gilbert Jack A , Zhu Yong-Guan , Ping Fan , Zhang Han-Luo
Published: July 2016

The overuse of antibiotics as veterinary feed additives is potentially contributing to a significant reservoir of antibiotic resistance in agricultural farmlands via the application of antibiotic-contaminated manure. Vermicomposting of swine manure using housefly larvae is a promising biotechnology for waste reduction and control of antibiotic pollution. To determine how vermicomposting influences antibiotic resistance traits in swine manure, we explored the resistome and associated bacterial community dynamics during larvae gut transit over 6 days of treatment. In total, 94 out of 158 antibiotic resistance genes (ARGs) were significantly attenuated (by 85%), while 23 were significantly enriched (3.9-fold) following vermicomposting. The manure-borne bacterial community showed a decrease in the relative abundance of Bacteroidetes, and an increase in Proteobacteria, specifically Ignatzschineria, following gut transit. ARG attenuation was significantly correlated with changes in microbial community succession, especially reduction in Clostridiales and Bacteroidales. Six genomes were assembled from the manure, vermicompost (final product) and gut samples, including Pseudomonas, Providencia, Enterococcus, Bacteroides and Alcanivorax. Transposon-linked ARGs were more abundant in gut-associated bacteria compared with those from manure and vermicompost. Further, ARG-transposon gene cassettes had a high degree of synteny between metagenomic assemblies from gut and vermicompost samples, highlighting the significant contribution of gut microbiota through horizontal gene transfer to the resistome of vermicompost. In conclusion, the larvae gut microbiome significantly influences manure-borne community succession and the antibiotic resistome during animal manure processing.
Non-equilibrium processing leads to record high thermoelectric figure of merit in PbTe–SrTe
Authors: Tan Gangjian , Shi Fengyuan , Hao Shiqiang , Zhao Li-Dong , Chi Hang , Zhang Xiaomi , Uher Ctirad , Wolverton Chris , Dravid Vinayak P. , Kanatzidis Mercouri G.
Published: July 2016

The broad-based implementation of thermoelectric materials in converting heat to electricity hinges on the achievement of high conversion efficiency. Here we demonstrate a thermoelectric figure of merit ZT of 2.5 at 923 K by the cumulative integration of several performance-enhancing concepts in a single material system. Using non-equilibrium processing we show that hole-doped samples of PbTe can be heavily alloyed with SrTe well beyond its thermodynamic solubility limit of <1 mol%. The much higher levels of Sr alloyed into the PbTe matrix widen the bandgap and create convergence of the two valence bands of PbTe, greatly boosting the power factors with maximal values over 30 μW cm−1 K−2. Exceeding the 5 mol% solubility limit leads to endotaxial SrTe nanostructures which produce extremely low lattice thermal conductivity of 0.5 W m−1 K−1 but preserve high hole mobilities because of the matrix/precipitate valence band alignment. The best composition is hole-doped PbTe–8%SrTe.
Sea ice and millennial-scale climate variability in the Nordic seas 90 kyr ago to present
Authors: Hoff Ulrike , Rasmussen Tine L. , Stein Ruediger , Ezat Mohamed M. , Fahl Kirsten
Published: July 2016

In the light of rapidly diminishing sea ice cover in the Arctic during the present atmospheric warming, it is imperative to study the distribution of sea ice in the past in relation to rapid climate change. Here we focus on glacial millennial-scale climatic events (Dansgaard/Oeschger events) using the sea ice proxy IP25 in combination with phytoplankton proxy data and quantification of diatom species in a record from the southeast Norwegian Sea. We demonstrate that expansion and retreat of sea ice varies consistently in pace with the rapid climate changes 90 kyr ago to present. Sea ice retreats abruptly at the start of warm interstadials, but spreads rapidly during cooling phases of the interstadials and becomes near perennial and perennial during cold stadials and Heinrich events, respectively. Low-salinity surface water and the sea ice edge spreads to the Greenland–Scotland Ridge, and during the largest Heinrich events, probably far into the Atlantic Ocean.
Observation of temperature-gradient-induced magnetization
Authors: Hou Dazhi , Qiu Zhiyong , Iguchi R. , Sato K. , Vehstedt E. K. , Uchida K. , Bauer G. E. W. , Saitoh E.
Published: July 2016

Applying magnetic fields has been the method of choice to magnetize non-magnetic materials, but they are difficult to focus. The magneto-electric effect and voltage-induced magnetization generate magnetization by applied electric fields, but only in special compounds or heterostructures. Here we demonstrate that a simple metal such as gold can be magnetized by a temperature gradient or magnetic resonance when in contact with a magnetic insulator by observing an anomalous Hall-like effect, which directly proves the breakdown of time-reversal symmetry. Such Hall measurements give experimental access to the spectral spin Hall conductance of the host metal, which is closely related to other spin caloritronics phenomena such as the spin Nernst effect and serves as a reference for theoretical calculation.
Phase-modulating lasers toward on-chip integration
Authors: Kurosaka Yoshitaka , Hirose Kazuyoshi , Sugiyama Takahiro , Takiguchi Yu , Nomoto Yoshiro
Published: July 2016

Controlling laser-beam patterns is indispensable in modern technology, where lasers are typically combined with phase-modulating elements such as diffractive optical elements or spatial light modulators. However, the combination of separate elements is not only a challenge for on-chip miniaturisation but also hinders their integration permitting the switchable control of individual modules. Here, we demonstrate the operation of phase-modulating lasers that emit arbitrarily configurable beam patterns without requiring any optical elements or scanning devices. We introduce a phase-modulating resonator in a semiconductor laser, which allows the concurrent realisation of lasing and phase modulation. The fabricated devices are on-chip-sized, making them suitable for integration. We believe this work will provide a breakthrough in various laser applications such as switchable illumination patterns for bio-medical applications, structured illuminations and even real three-dimensional or highly realistic displays, which cannot be realised with simple combinations of conventional devices or elements.
Glycerol Monolaurate (GML) inhibits human T cell signaling and function by disrupting lipid dynamics
Authors: Zhang Michael S. , Sandouk Aline , Houtman Jon C. D.
Published: July 2016

Glycerol Monolaurate (GML) is a naturally occurring fatty acid widely utilized in food, cosmetics, and homeopathic supplements. GML is a potent antimicrobial agent that targets a range of bacteria, fungi, and enveloped viruses but select findings suggest that GML also has immunomodulatory functions. In this study, we have mechanistically examined if GML affects the signaling and functional output of human primary T cells. We found that GML potently altered order and disorder dynamics in the plasma membrane that resulted in reduced formation of LAT, PLC-γ, and AKT microclusters. Altered membrane events induced selective inhibition of TCR-induced phosphorylation of regulatory P85 subunit of PI3K and AKT as well as abrogated calcium influx. Ultimately, GML treatment potently reduced TCR-induced production of IL-2, IFN-γ, TNF-α, and IL-10. Our data reveal that the widely used anti-microbial agent GML also alters the lipid dynamics of human T cells, leading to their defective signaling and function.
The right temporoparietal junction encodes efforts of others during action observation
Authors: Mizuguchi Nobuaki , Nakata Hiroki , Kanosue Kazuyuki
Published: July 2016

Smooth social interactions require a deep understanding of others’ intentions and feelings. In the present study, to investigate brain regions that respond to inference of others’ effort level, we recorded brain activity during action observation of different effort levels using functional magnetic resonance imaging (fMRI). We used a dumbbell curl movement to depict a movement requiring effort. To dissociate the factors of effort level of the actor and weight of the dumbbell, we used four combinations of dumbbell weight and actor physique: a thin actor or a built actor lifting a heavy or light dumbbell. During observation of dumbbell curls, the bilateral front-parietal action observation network (AON) was activated. This included the premotor cortices, parietal cortices, visual areas 5/superior temporal cortices (STS), amygdalae, hippocampi, right dorsolateral and ventrolateral frontal cortices. When we evaluated brain regions associated with the actor’s effort level, activity in the right temporoparietal junction (TPJ) and STS was observed. However, activity in the front-parietal AON was independent of the actor’s effort during action observation. This finding suggests that the right TPJ and STS play an important role in the inference of others’ effort levels during the observation of others’ movements.
Changes in the folding landscape of the WW domain provide a molecular mechanism for an inherited genetic syndrome
Authors: Pucheta-Martinez Encarna , D’Amelio Nicola , Lelli Moreno , Martinez-Torrecuadrada Jorge L. , Sudol Marius , Saladino Giorgio , Gervasio Francesco Luigi
Published: July 2016

WW domains are small domains present in many human proteins with a wide array of functions and acting through the recognition of proline-rich sequences. The WW domain belonging to polyglutamine tract-binding protein 1 (PQBP1) is of particular interest due to its direct involvement in several X chromosome-linked intellectual disabilities, including Golabi-Ito-Hall (GIH) syndrome, where a single point mutation (Y65C) correlates with the development of the disease. The mutant cannot bind to its natural ligand WBP11, which regulates mRNA processing. In this work we use high-field high-resolution NMR and enhanced sampling molecular dynamics simulations to gain insight into the molecular causes the disease. We find that the wild type protein is partially unfolded exchanging among multiple beta-strand-like conformations in solution. The Y65C mutation further destabilizes the residual fold and primes the protein for the formation of a disulphide bridge, which could be at the origin of the loss of function.
Aberrant DNA methylation reprogramming in bovine SCNT preimplantation embryos
Authors: Zhang Sheng , Chen Xin , Wang Fang , An Xinglan , Tang Bo , Zhang Xueming , Sun Liguang , Li Ziyi
Published: July 2016

DNA methylation reprogramming plays important roles in mammalian embryogenesis. Mammalian somatic cell nuclear transfer (SCNT) embryos with reprogramming defects fail to develop. Thus, we compared DNA methylation reprogramming in preimplantation embryos from bovine SCNT and in vitro fertilization (IVF) and analyzed the influence of vitamin C (VC) on the reprogramming of DNA methylation. The results showed that global DNA methylation followed a typical pattern of demethylation and remethylation in IVF preimplantation embryos; however, the global genome remained hypermethylated in SCNT preimplantation embryos. Compared with the IVF group, locus DNA methylation reprogramming showed three patterns in the SCNT group. First, some pluripotency genes (POU5F1 and NANOG) and repeated elements (satellite I and α-satellite) showed insufficient demethylation and hypermethylation in the SCNT group. Second, a differentially methylated region (DMR) of an imprint control region (ICR) in H19 exhibited excessive demethylation and hypomethylation. Third, some pluripotency genes (CDX2 and SOX2) were hypomethylated in both the IVF and SCNT groups. Additionally, VC improved the DNA methylation reprogramming of satellite I, α-satellite and H19 but not that of POU5F1 and NANOG in SCNT preimplantation embryos. These results indicate that DNA methylation reprogramming was aberrant and that VC influenced DNA methylation reprogramming in SCNT embryos in a locus-specific manner.
Post-Mortem Corneal Thickness Measurements with a Portable Optical Coherence Tomography System: a Reliability Study
Authors: Napoli Pietro Emanuele , Nioi Matteo , d’Aloja Ernesto , Fossarello Maurizio
Published: July 2016

The purpose of this study was to determine the repeatability and reproducibility of post-mortem central corneal thickness (CCT) measurements by using a real-time, portable optical coherence tomography (OCT) system on an animal model and to prospectively evaluate the time-course of post-mortem changes in CCT. Forty-six ocular globes of sheep (Ovis aries) were analyzed with a portable spectral-domain OCT device by two operators at different postmortem intervals (PMIs) as follows: immediately (i.e. within 10 minutes), at the 30th minute, at the 1st, 6th, 12th, 24th and 48th hour and later (up to the 96th hour). The coefficient of repeatability ranged from 0.3% to 3.5% and coefficients of reproducibility ranged from 0.2% to 3.7% in the central region of the cornea. The intraclass correlation coefficients were particularly high at different PMIs, thus confirming good measurement reliability with the portable OCT. The average CCT decreased immediately and then increased thereafter, with two peaks at 6 and 24 hours after death. Our results suggest that portable OCT is a reliable tool for monitoring CCT variations after death and may be useful in characterizing corneas before explantation, detecting quantitative variations during post-mortem corneal degeneration or assessing changes in CCT for forensic implications.
Sulforhodamine 101, a widely used astrocyte marker, can induce cortical seizure-like activity at concentrations commonly used
Authors: Rasmussen Rune , Nedergaard Maiken , Petersen Nicolas Caesar
Published: July 2016

Sulforhodamine 101 (SR101) is a preferential astrocyte marker widely used in 2-photon microscopy experiments. Here we show, that topical loading of two commonly used SR101 concentrations, 100 μM and 250 μM when incubated for 10 min, can induce seizure-like local field potential (LFP) activity in both anaesthetized and awake mouse sensori-motor cortex. This cortical seizure-like activity develops in less than ten minutes following topical loading and when applied longer, these neuronal discharges reliably evoke contra-lateral hindlimb muscle contractions. Short duration (<1 min) incubation of 100 μM and 250 μM SR101 or application of lower concentrations 25 μM and 50 μM of SR101, incubated for 30 and 20 min, respectively, did not induce abnormal LFP activity in sensori-motor cortex, but did label astrocytes and may thus be considered more appropriate concentrations for in vivo astrocyte labeling. In addition to label astrocytes SR101 may, at 100 μM and 250 μM, induce abnormal neuronal activity and interfere with cortical circuit activity. SR101 concentration of 50 μM or lower did not induce abnormal neuronal activity. We advocate that, to label astrocytes with SR101, concentrations no higher than 50 μM should be used for in vivo experiments.
Hypoxia induced the differentiation of Tbx18-positive epicardial cells to CoSMCs
Authors: Jing Xiaodong , Gao Yulin , Xiao Songlin , Qin Qin , Wei Xiaoming , Yan Yuling , Wu Ling , Deng Songbai , Du Jianlin , Liu Yajie , She Qiang
Published: July 2016

Understanding the origin and differentiation mechanism of coronary vascular smooth muscle cells (CoSMCs) is very important to cardiovascular biology. The early cardiovascular system is formed in a hypoxic microenvironment and Tbx18-positive epicardial cells are a source of CoSMCs. However, the effects of hypoxia on the differentiation of Tbx18-positive epicardial cells to CoSMCs and the primary regulatory mechanism are insufficiently understood. Using Tbx18:Cre/R26REYFP/LacZ fate-tracing mice, we cultured highly purified Tbx18-positive epicardial cells. We further showed that hypoxia induced Tbx18-positive epicardial cells to differentiate into CoSMCs and promoted the epithelial-mesenchymal transition (EMT) process of the cells in vitro. The induction of differentiation was primarily achieved via the hypoxia inducible factor-1α (HIF-1α)-mediated effects exerted on Snail. Using a cell migration assay, we showed that hypoxia enhanced the motility of Tbx18-positive epicardial cells. By constructing a hypoxic model of the embryonic epicardium in vivo, we showed that hypoxia led to premature in situ differentiation of Tbx18-positive epicardial cells to CoSMCs. Furthermore, hypoxia was sufficient to induce Snail expression in Tbx18-positive epicardial cells in vivo. Our study suggests that hypoxia intervention was sufficient to induce the differentiation of Tbx18-positive epicardial cells to CoSMCs. Furthermore, this differentiation was achieved primarily via HIF-1α-mediated regulation of Snail.
SOX9 is a novel cancer stem cell marker surrogated by osteopontin in human hepatocellular carcinoma
Authors: Kawai Takayuki , Yasuchika Kentaro , Ishii Takamichi , Miyauchi Yuya , Kojima Hidenobu , Yamaoka Ryoya , Katayama Hokahiro , Yoshitoshi Elena Yukie , Ogiso Satoshi , Kita Sadahiko , Yasuda Katsutaro , Fukumitsu Ken , Komori Junji , Hatano Etsuro , Kawaguchi Yoshiya , Uemoto Shinji
Published: July 2016

The current lack of cancer stem cell (CSC) markers that are easily evaluated by blood samples prevents the establishment of new therapeutic strategies in hepatocellular carcinoma (HCC). Herein, we examined whether sex determining region Y-box 9 (SOX9) represents a new CSC marker and whether osteopontin (OPN) can be used as a surrogate marker of SOX9 in HCC. In HCC cell lines transfected with a SOX9 promoter-driven enhanced green fluorescence protein gene, FACS-isolated SOX9+ cells were capable of self-renewal and differentiation into SOX9− cells and displayed high proliferation capacity in vitro. Xenotransplantation experiments revealed that SOX9+ cells reproduced, differentiated into SOX9− cells and generated tumors at a high frequency in vivo. Moreover, SOX9+ cells were found to be involved in epithelial-mesenchymal transition (EMT) and activation of TGFb/Smad signaling. Gain/loss of function experiments showed that SOX9 regulates Wnt/beta-catenin signaling, including cyclin D1 and OPN. Immunohistochemistry of 166 HCC surgical specimens and serum OPN measurements showed that compared to SOX9− patients, SOX9+ patients had significantly poorer recurrence-free survival, stronger venous invasion and higher serum OPN levels. In conclusion, SOX9 is a novel HCC-CSC marker regulating the Wnt/beta-catenin pathway and its downstream target, OPN. OPN is a useful surrogate marker of SOX9 in HCC.
Controlling the phase locking of stochastic magnetic bits for ultra-low power computation
Authors: Mizrahi Alice , Locatelli Nicolas , Lebrun Romain , Cros Vincent , Fukushima Akio , Kubota Hitoshi , Yuasa Shinji , Querlioz Damien , Grollier Julie
Published: July 2016

When fabricating magnetic memories, one of the main challenges is to maintain the bit stability while downscaling. Indeed, for magnetic volumes of a few thousand nm3, the energy barrier between magnetic configurations becomes comparable to the thermal energy at room temperature. Then, switches of the magnetization spontaneously occur. These volatile, superparamagnetic nanomagnets are generally considered useless. But what if we could use them as low power computational building blocks? Remarkably, they can oscillate without the need of any external dc drive and despite their stochastic nature, they can beat in unison with an external periodic signal. Here we show that the phase locking of superparamagnetic tunnel junctions can be induced and suppressed by electrical noise injection. We develop a comprehensive model giving the conditions for synchronization and predict that it can be achieved with a total energy cost lower than 10−13 J. Our results open the path to ultra-low power computation based on the controlled synchronization of oscillators.
Impaired fornix–hippocampus integrity is linked to peripheral glutathione peroxidase in early psychosis
Authors: Baumann P S , Griffa A , Fournier M , Golay P , Ferrari C , Alameda L , Cuenod M , Thiran J-P , Hagmann P , Do K Q , Conus P
Published: July 2016

Several lines of evidence implicate the fornix–hippocampus circuit in schizophrenia. In early-phase psychosis, this circuit has not been extensively investigated and the underlying mechanisms affecting the circuit are unknown. The hippocampus and fornix are vulnerable to oxidative stress at peripuberty in a glutathione (GSH)-deficient animal model. The purposes of the current study were to assess the integrity of the fornix–hippocampus circuit in early-psychosis patients (EP), and to study its relationship with peripheral redox markers. Diffusion spectrum imaging and T1-weighted magnetic resonance imaging (MRI) were used to assess the fornix and hippocampus in 42 EP patients compared with 42 gender- and age-matched healthy controls. Generalized fractional anisotropy (gFA) and volumetric properties were used to measure fornix and hippocampal integrity, respectively. Correlation analysis was used to quantify the relationship of gFA in the fornix and hippocampal volume, with blood GSH levels and glutathione peroxidase (GPx) activity. Patients compared with controls exhibited lower gFA in the fornix as well as smaller volume in the hippocampus. In EP, but not in controls, smaller hippocampal volume was associated with high GPx activity. Disruption of the fornix–hippocampus circuit is already present in the early stages of psychosis. Higher blood GPx activity is associated with smaller hippocampal volume, which may support a role of oxidative stress in disease mechanisms.
Low temperature excitonic spectroscopy and dynamics as a probe of quality in hybrid perovskite thin films
Authors: Sarang Som , Ishihara Hidetaka , Chen Yen-Chang , Lin Oliver , Gopinathan Ajay , Tung Vincent C. , Ghosh Sayantani
Published: July 2016

The low temperature anomalous spectroscopic properties of hybrid perovskite thin films were analyzed and a theoretical formalism was developed to quantify perovskite film quality.
Merocyanine 540 adsorbed on polyethylenimine-functionalized graphene oxide nanocomposites as a turn-on fluorescent sensor for bovine serum albumin
Authors: Bayraktutan Tuğba , Meral Kadem
Published: July 2016

We suggest a simple, fast, sensitive and selective BSA sensor designed by assembling MC540 molecules on PEI–GO nanocomposites.
A robust salt-tolerant superoleophobic aerogel inspired by seaweed for efficient oil–water separation in marine environments
Authors: Li Yuqi , Zhang Hui , Fan Mizi , Zhuang Jiandong , Chen Lihui
Published: July 2016

A robust salt-tolerant superoleophobic aerogel was fabricated by a simple combined freeze-drying and ionic cross-linking method for oil–seawater separation.
The dietary effect of milk sphingomyelin on the lipid metabolism of obese/diabetic KK-Aymice and wild-type C57BL/6J mice
Authors: Yamauchi Ippei , Uemura Mariko , Hosokawa Masashi , Iwashima-Suzuki Ai , Shiota Makoto , Miyashita Kazuo
Published: July 2016

Purified milk sphingomyelin (SM) was obtained from lipid concentrated butter serum (LC-BS) by successive separations involving solvent fractionation, selective saponification, and silicic acid column chromatography.
Mentha spicata L. infusions as sources of antioxidant phenolic compounds: emerging reserve lots with special harvest requirements
Authors: Rita Ingride , Pereira Carla , Barros Lillian , Santos-Buelga Celestino , Ferreira Isabel C. F. R.
Published: July 2016

Infusions of Mentha spicata reserve lots revealed the highest total phenolic compound content and, consequently, the mightiest antioxidant activity.
Anti-platelet and anti-thrombogenic effects of shikimic acid in sedentary population
Authors: Veach Daniel , Hosking Holly , Thompson Kiara , Santhakumar Abishek Bommannan
Published: July 2016

Thisex vivostudy was performed to evaluate the anti-platelet and anti-thrombogenic potential of shikimic acid (SA), a plant phenolic metabolite.
Acetate ions enhance load and stability of doxorubicin onto PEGylated nanodiamond for selective tumor intracellular controlled release and therapy
Authors: Li Lin , Tian Lu , Zhao Wenjing , Li Yingqi , Yang Binsheng
Published: July 2016

A successful drug delivery device for cancer chemotherapy should ideally be able to load drugs highly, bring the drug preferentially into tumor cells and reduce its distribution in normal tissue to enhance therapeutic efficacy.
Nanoscale mechanics guides cellular decision making
Authors: Rahil Zainab , Pedron Sara , Wang Xuefeng , Ha TaekJip , Harley Brendan , Leckband Deborah
Published: July 2016

Nanoscale tension gauges revealed how substrate stiffness alters pico Newton force thresholds that trigger initial cell attachment, spreading, and adhesion maturation.
Accurate quantification of selenoproteins in human plasma/serum by isotope dilution ICP-MS: focus on selenoprotein P
Authors: Busto M. Estela del Castillo , Oster Caroline , Cuello-Nuñez Susana , Deitrich Christian L. , Raab Andrea , Konopka Anna , Lehmann Wolf D. , Goenaga-Infante Heidi , Fisicaro Paola
Published: July 2016

Systematic approach for the accurate quantification of selenoproteins (SEPP1) in human plasma/serum by IDA-LC-ICP-MS.
Organometallic derivatives of natural products: dicobalt hexacarbonyl complexes of geranyl-alkynes
Authors: Moore Angela , Ostermann Johannes , Ortin Yannick , McGlinchey Michael J.
Published: July 2016

Di- and tri-cobalt carbonyl clusters bearing geranyl or neryl substituents offer potential routes to novel terpenoid systems.
A Ni1−xZnxS/Ni foam composite electrode with multi-layers: one-step synthesis and high supercapacitor performance
Authors: Wang Xiaobing , Hao Jin , Su Yichang , Liu Fanggang , An Jian , Lian Jianshe
Published: July 2016

Multi-layer NixZn1−xS/Ni foam composites were synthesized by a one-step hydrothermal reaction generating in situ growth on the Ni foam. The doping of Zn into the NixZn1−xS/Ni composite constructs the multi-layer nanostructure. The as-fabricated Ni1−xZnxS/Ni foam-2 h supercapacitor electrode shows outstanding rate properties.
Synthesis of Co–Sn intermetallic nanocatalysts toward selective hydrogenation of citral
Authors: Zhou Junyao , Yang Yusen , Li Changming , Zhang Shitong , Chen Yudi , Shi Shuxian , Wei Min
Published: July 2016

Three Co–Sn intermetallic compound catalysts are prepared via a hydrotalcite approach, which show satisfactory catalytic performance toward selective hydrogenation of citral.
Efficient water oxidation through strongly coupled graphitic C3N4 coated cobalt hydroxide nanowires
Authors: Tahir Muhammad , Mahmood Nasir , Pan Lun , Huang Zhen-Feng , Lv Zhe , Zhang Jingwen , Butt Faheem. K. , Shen Guoqiang , Zhang Xiangwen , Dou Shi Xue , Zou Ji-Jun
Published: July 2016

The activation of redox sites of Co(OH)2 by coating g-C3N4 brings outstanding over potential of 320 mV at 10 mA cm−2 and outperforms IrO2 and RuO2 along with best reported Co and g-C3N4 based catalyst.
Zinc-stabilized colloidal polyelectrolyte complexes of chitosan/hyaluronan: a tool for the inhibition of HIV-1 infection
Authors: Wu Danjun , Ensinas Agathe , Verrier Bernard , Primard Charlotte , Cuvillier Armelle , Champier Gaël , Paul Stephane , Delair Thierry
Published: July 2016

Zinc(ii) stabilized polyelectrolyte nano-complexes (PECs) of chitosan and hyaluronan (HYA) were designed as safe and efficient drug delivery systems.
Effects of alloying on the optical properties of organic–inorganic lead halide perovskite thin films
Authors: Ndione Paul F. , Li Zhen , Zhu Kai
Published: July 2016

Spectroscopic ellipsometry analysis of optical transitions and optical constants in hybrid organic–inorganic perovskite alloys.
TRPV6 modulates proliferation of human pancreatic neuroendocrine BON-1 tumour cells
Authors: Skrzypski Marek , Kołodziejski Paweł A. , Mergler Stefan , Khajavi Noushafarin , Nowak Krzysztof W. , Strowski Mathias Z.
Published: July 2016

Highly Ca2+ permeable receptor potential channel vanilloid type 6 (TRPV6) modulates a variety of biological functions including calcium-dependent cell growth and apoptosis. So far, the role of TRPV6 in controlling growth of pancreatic neuroendocrine tumour (NET) cells is unknown. In the present study, we characterize the expression of TRPV6 in pancreatic BON-1 and QGP-1 NET cells. Furthermore, we evaluate the impact of TRPV6 on intracellular calcium, the activity of nuclear factor of activated T-cells (NFAT) and proliferation of BON-1 cells. TRPV6 expression was assessed by real-time PCR and Western blot. TRPV6 mRNA expression and protein production were down-regulated by siRNA. Changes in intracellular calcium levels were detected by fluorescence calcium imaging (fura-2/AM). NFAT activity was studied by NFAT reporter assay; cell proliferation by bromodeoxyuridine (BrdU), MTT and propidium iodine staining. TRPV6 mRNA and protein are present in BON-1 and QGP-1 NET-cells. Down-regulation of TRPV6 attenuates BON-1 cell proliferation. TRPV6 down-regulation is associated with decreased Ca2+ response pattern and reduced NFAT activity. In conclusion, TRPV6 is expressed in pancreatic NETs and modulates cell proliferation via Ca2+-dependent mechanism, which is accompanied by NFAT activation.