bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences in sheep and goats milk microbiological profile between conventional and organic farming systems in Greece
Authors: Malissiova Eleni , Papadopoulos Theofilos , Kyriazi Aikaterini , Mparda Maria , Sakorafa Christina , Katsioulis Antonios , Katsiaflaka Anna , Kyritsi Maria , Zdragas Antonios , Hadjichristodoulou Christos
Published: March 2017

The aim of this study was to examine differences in the microbiological profile and antimicrobial resistance of bacteria isolated from milk from organic and conventional sheep and goat farms. Twenty-five organic and 25 conventional sheep and goat farms in the region of Thessaly, Greece participated in this study. A standardised detailed questionnaire was used to describe farming practices. A total of 50 samples were collected and analysed for total viable count (TVC), total coliform count (TCC) and somatic cell count (SCC), whileStaphylococcus aureusandEscherichia coliwere isolated using standard methods. Isolates were identified at species level by Api-test and Matrix-Assisted Laser Desorption/Ionisation-Time of Flight Mass Spectrometry (MALDI-TOF MS). Susceptibility to a panel of 20 forE. coliand 16 forS. aureusantimicrobials was determined by the agar dilution method. Pulsed Field Gel Electrophoresis (PFGE) was performed forS. aureusandE. coliisolates to determine predominant clones. Lower counts of TVC, TCC and SCC were identified in milk from the organic farms, possibly due to differences in the hygienic farming practices found on those farms. API-tests and MALDI-TOF MS showed no significant differences in theS. aureusandE. coliisolates. Overall, antimicrobial resistance rates were low, while a statistically higher percentage was estimated among strains originating from conventional farms in comparison with organic farms, possibly due to the restriction of antibiotic use in organic farming. PFGE revealed diversity amongS. aureusandE. colipopulations in both organic and conventional farms indicating circulation of 2–3 main clones changing slightly during their evolution. Consequently, there is evidence that milk from the organic farms presents a better microbiological profile when compared with milk from conventional farms.
A large outbreak of acute gastroenteritis in Shippensburg, Pennsylvania, 1972 revisited: evidence for common source exposure to a recombinant GII.Pg/GII.3 norovirus
Authors: JOHNSON J. A. , PARRA G. I. , LEVENSON E. A. , GREEN K. Y.
Published: March 2017

Historical outbreaks can be an important source of information in the understanding of norovirus evolution and epidemiology. Here, we revisit an outbreak of undiagnosed gastroenteritis that occurred in Shippensburg, Pennsylvania in 1972. Nearly 5000 people fell ill over the course of 10 days. Symptoms included diarrhea, vomiting, stomach cramps, and fever, lasting for a median of 24 h. Using current techniques, including next-generation sequencing of full-length viral genomic amplicons, we identified an unusual norovirus recombinant (GII.Pg/GII.3) in nine of 15 available stool samples from the outbreak. This particular recombinant virus has not been reported in recent decades, although GII.3 and GII.Pg genotypes have been detected individually in current epidemic strains. The consensus nucleotide sequences were nearly identical among the four viral genomes analysed, although each strain had three to seven positions in the genome with heterogenous non-synonymous nucleotide subpopulations. Two of these resulting amino acid polymorphisms were conserved in frequency among all four cases, consistent with common source exposure and successful transmission of a mixed viral population. Continued investigation of variant nucleotide populations and recombination events among ancestral norovirus strains such as the Shippensburg virus may provide unique insight into the origin of contemporary strains.
An update on diet and nutritional factors in systemic lupus erythematosus management
Authors: Aparicio-Soto Marina , Sánchez-Hidalgo Marina , Alarcón-de-la-Lastra Catalina
Published: March 2017

Systemic lupus erythematosus (SLE) is a chronic inflammatory and autoimmune disease characterised by multiple organ involvement and a large number of complications. SLE management remains complicated owing to the biological heterogeneity between patients and the lack of safe and specific targeted therapies. There is evidence that dietary factors can contribute to the geoepidemiology of autoimmune diseases such as SLE. Thus, diet therapy could be a promising approach in SLE owing to both its potential prophylactic effects, without the side effects of classical pharmacology, and its contribution to reducing co-morbidities and improving quality of life in patients with SLE. However, the question arises as to whether nutrients could ameliorate or exacerbate SLE and how they could modulate inflammation and immune function at a molecular level. The present review summarises preclinical and clinical experiences to provide the reader with an update of the positive and negative aspects of macro- and micronutrients and other nutritional factors, including dietary phenols, on SLE, focusing on the mechanisms of action involved.
A Discussion of Alexander Cooley and Jack Snyder's Ranking the World: Grading States as a Tool for Global Governance
Authors: Schmitter Philippe C.
Published: March 2017

Ranking the World: Grading States as a Tool of Global Governance, edited by Alexander Cooley and Jack Snyder, assembles an impressive group of political scientists to critically discuss “the important analytical, normative, and policy issues associated with the contemporary practice of ‘grading states.’” The volume addresses a topic of importance to a wide range of political scientists in comparative politics, international relations, and political theory, and raises some fundamental questions about the role of political science at the nexus of theory and practice. We have thus invited a number of colleagues to discuss the volume and its broader implications for political science inquiry.
Taxation of Cross-Border Transfers of Carbon Emission Allowances under Linked Emissions Trading Schemes
Authors: Black Celeste M.
Published: March 2017

Economic arguments in support of linking emissions trading schemes suggest that such linking could provide access to lower cost abatement options and increase market stability. The decisions of whether and how to link emissions trading schemes often focus on the design features of the relevant schemes, but an additional factor which has the potential to undermine the efficiency of linked schemes is taxation. This article systematically tests two alternative approaches to the direct (income) taxation of cross-border transfers of emission allowances for differential tax outcomes. Four hypothetical transactions are considered under three different linking mechanisms and on the assumption that a tax treaty based on the OECD Model Tax Convention on Income and on Capital is in force. This analysis evidences that, in some cases – and especially if the relevant jurisdictions adopt different approaches to the taxation of allowance transactions under domestic law – there is the potential for timing differences or double taxation that could impact on the efficiency of the linked trading schemes. It is therefore important for tax implications to be considered as part of any linking proposal.
Glucose Increases Risky Behavior and Attitudes in People Low in	Self-Control
Authors: Pfundmair Michaela , Lermer Eva , Frey Dieter
Published: March 2017

Abstract. People low in self-control have a strong proclivity toward risk-taking. Risk-taking behavior provides an opportunity to obtain some form of reward. Glucose, on the other hand, seems to facilitate reward and goal-directed behavior. In a pilot study executed in the laboratory, we investigated whether consuming a glucose drink would increase risky behavior and attitudes in people low in self-control. Our findings revealed that a dose of glucose compared to placebo increased risk-taking on a behavioral and cognitive level in participants low in self-control but not in participants high in self-control. The findings may shed some light on the psychological underpinnings of glucose: By showing glucose’s association with high-risk behavior, they support the assumption of glucose driving a goal-directed motivation.
Clinical, cellular, microscopic, and ultrastructural studies of a case of fibrogenesis imperfecta ossium
Authors: Barron Melissa L , Rybchyn Mark S , Ramesh Sutharshani , Mason Rebecca S , Fiona Bonar S , Stalley Paul , Khosla Sundeep , Hudson Bernie , Arthur Christopher , Kim Edward , Clifton-Bligh Roderick J , Clifton-Bligh Phillip B
Published: March 2017

Fibrogenesis imperfecta ossium is a rare disorder of bone usually characterized by marked osteopenia and associated with variable osteoporosis and osteosclerosis, changing over time. Histological examination shows that newly formed collagen is abnormal, lacking birefringence when examined by polarized light. The case presented demonstrates these features and, in addition, a previously undocumented finding of a persistent marked reduction of the serum C3 and C4. Osteoblasts established in culture from a bone biopsy showed abnormal morphology on electron microscopy and increased proliferation when cultured with benzoylbenzoyl-ATP and 1,25-dihydroxyvitamin D, contrasting with findings in normal osteoblasts in culture. A gene microarray study showed marked upregulation of the messenger RNA (mRNA) for G-protein-coupled receptor 128 (GPR 128), an orphan receptor of unknown function and also of osteoprotegerin in the patient’s osteoblasts in culture. When normal osteoblasts were cultured with the patient’s serum, there was marked upregulation of the mRNA for aquaporin 1. A single pathogenetic factor to account for the features of this disorder has not been defined, but the unique findings described here may facilitate more definitive investigation of the abnormal bone cell function.
Imaging to study solid tumour origin and progression: lessons from research and clinical oncology
Authors: Raimondo Stefania , Zito Giovanni
Published: March 2017

Biomedical imaging in recent decades has clarified our understanding of normal and pathological cellular processes in vivo. In particular, this approach recently provided insights into processes occurring at a molecular or genetic level rather than at the anatomical level. The evolution of this discipline by engineering have led to its integration into biomedical research to (1) increase sensitivity and resolution imaging and to (2) improve tissue and cell specificity. Currently, imaging approaches are used in three different biomedical areas: (a) identification of cellular processes in physiological and disease state; (b) in vivo single‐cell imaging; and (c) identification of new prognostic and therapeutical strategies. In this review, we will focus on the state of art of biomedical imaging in cancer. Specifically, we will highlight the most important advances in imaging tools available for basic and translational cancer research, with a particular emphasis on solid tissue malignancies.
Phosphorylation of Rab-coupling protein by LMTK3 controls Rab14-dependent EphA2 trafficking to promote cell:cell repulsion
Authors: Gundry Christine , Marco Sergi , Rainero Elena , Miller Bryan , Dornier Emmanuel , Mitchell Louise , Caswell Patrick T. , Campbell Andrew D. , Hogeweg Anna , Sansom Owen J. , Morton Jennifer P. , Norman Jim C.
Published: March 2017

The Rab GTPase effector, Rab-coupling protein (RCP) is known to promote invasive behaviour in vitro by controlling integrin and receptor tyrosine kinase (RTK) trafficking, but how RCP influences metastasis in vivo is unclear. Here we identify an RTK of the Eph family, EphA2, to be a cargo of an RCP-regulated endocytic pathway which controls cell:cell repulsion and metastasis in vivo. Phosphorylation of RCP at Ser435 by Lemur tyrosine kinase-3 (LMTK3) and of EphA2 at Ser897 by Akt are both necessary to promote Rab14-dependent (and Rab11-independent) trafficking of EphA2 which generates cell:cell repulsion events that drive tumour cells apart. Genetic disruption of RCP or EphA2 opposes cell:cell repulsion and metastasis in an autochthonous mouse model of pancreatic adenocarcinoma—whereas conditional knockout of another RCP cargo, α5 integrin, does not suppress pancreatic cancer metastasis—indicating a role for RCP-dependent trafficking of an Eph receptor to drive tumour dissemination in vivo.
Ground state selection under pressure in the quantum pyrochlore magnet Yb2Ti2O7
Authors: Kermarrec E. , Gaudet J. , Fritsch K. , Khasanov R. , Guguchia Z. , Ritter C. , Ross K. A. , Dabkowska H. A. , Gaulin B. D.
Published: March 2017

A quantum spin liquid is a state of matter characterized by quantum entanglement and the absence of any broken symmetry. In condensed matter, the frustrated rare-earth pyrochlore magnets Ho2Ti2O7 and Dy2Ti2O7, so-called spin ices, exhibit a classical spin liquid state with fractionalized thermal excitations (magnetic monopoles). Evidence for a quantum spin ice, in which the magnetic monopoles become long range entangled and an emergent quantum electrodynamics arises, seems within reach. The magnetic properties of the quantum spin ice candidate Yb2Ti2O7 have eluded a global understanding and even the presence or absence of static magnetic order at low temperatures is controversial. Here we show that sensitivity to pressure is the missing key to the low temperature behaviour of Yb2Ti2O7. By combining neutron diffraction and muon spin relaxation on a stoichiometric sample under pressure, we evidence a magnetic transition from a disordered, non-magnetic, ground state to a splayed ferromagnetic ground state.
Comparative genomics reveals contraction in olfactory receptor genes in bats
Authors: Tsagkogeorga Georgia , Müller Steven , Dessimoz Christophe , Rossiter Stephen J.
Published: March 2017

Gene loss and gain during genome evolution are thought to play important roles in adaptive phenotypic diversification. Among mammals, bats possess the smallest genomes and have evolved the unique abilities of powered flight and laryngeal echolocation. To investigate whether gene family evolution has contributed to the genome downsizing and phenotypic diversification in this group, we performed comparative evolutionary analyses of complete proteome data for eight bat species, including echolocating and non-echolocating forms, together with the proteomes of 12 other laurasiatherian mammals. Our analyses revealed extensive gene loss in the most recent ancestor of bats, and also of carnivores (both >1,000 genes), although this gene contraction did not appear to correlate with the reduction in genome size in bats. Comparisons of highly dynamic families suggested that expansion and contraction affected genes with similar functions (immunity, response to stimulus) in all laurasiatherian lineages. However, the magnitude and direction of these changes varied greatly among groups. In particular, our results showed contraction of the Olfactory Receptor (OR) gene repertoire in the last common ancestor of all bats, as well as that of the echolocating species studied. In contrast, non-echolocating fruit bats showed evidence of expansion in ORs, supporting a “trade-off” between sensory modalities.
Robust Analysis of Fluxes in Genome-Scale Metabolic Pathways
Authors: MacGillivray Michael , Ko Amy , Gruber Emily , Sawyer Miranda , Almaas Eivind , Holder Allen
Published: March 2017

Constraint-based optimization, such as flux balance analysis (FBA), has become a standard systems-biology computational method to study cellular metabolisms that are assumed to be in a steady state of optimal growth. The methods are based on optimization while assuming (i) equilibrium of a linear system of ordinary differential equations, and (ii) deterministic data. However, the steady-state assumption is biologically imperfect, and several key stoichiometric coefficients are experimentally inferred from situations of inherent variation. We propose an approach that explicitly acknowledges heterogeneity and conducts a robust analysis of metabolic pathways (RAMP). The basic assumption of steady state is relaxed, and we model the innate heterogeneity of cells probabilistically. Our mathematical study of the stochastic problem shows that FBA is a limiting case of our RAMP method. Moreover, RAMP has the properties that: A) metabolic states are (Lipschitz) continuous with regards to the probabilistic modeling parameters, B) convergent metabolic states are solutions to the deterministic FBA paradigm as the stochastic elements dissipate, and C) RAMP can identify biologically tolerable diversity of a metabolic network in an optimized culture. We benchmark RAMP against traditional FBA on genome-scale metabolic reconstructed models of E. coli, calculating essential genes and comparing with experimental flux data.
An RNA nanoparticle vaccine against Zika virus elicits antibody and CD8+ T cell responses in a mouse model
Authors: Chahal Jasdave S. , Fang Tao , Woodham Andrew W. , Khan Omar F. , Ling Jingjing , Anderson Daniel G. , Ploegh Hidde L.
Published: March 2017

The Zika virus (ZIKV) outbreak in the Americas and South Pacific poses a significant burden on human health because of ZIKV’s neurotropic effects in the course of fetal development. Vaccine candidates against ZIKV are coming online, but immunological tools to study anti-ZIKV responses in preclinical models, particularly T cell responses, remain sparse. We deployed RNA nanoparticle technology to create a vaccine candidate that elicited ZIKV E protein-specific IgG responses in C57BL/6 mice as assayed by ELISA. Using this tool, we identified a unique H-2Db-restricted epitope to which there was a CD8+T cell response in mice immunized with our modified dendrimer-based RNA nanoparticle vaccine. These results demonstrate that this approach can be used to evaluate new candidate antigens and identify immune correlates without the use of live virus.
Simulation-assisted design of microfluidic sample traps for optimal trapping and culture of non-adherent single cells, tissues, and spheroids
Authors: Rousset Nassim , Monet Frédéric , Gervais Thomas
Published: March 2017

This work focuses on modelling design and operation of “microfluidic sample traps” (MSTs). MSTs regroup a widely used class of microdevices that incorporate wells, recesses or chambers adjacent to a channel to individually trap, culture and/or release submicroliter 3D tissue samples ranging from simple cell aggregates and spheroids, toex vivotissue samples and other submillimetre-scale tissue models. Numerous MST designs employing various trapping mechanisms have been proposed in the literature, spurring the development of 3D tissue models for drug discovery and personalized medicine. Yet, there lacks a general framework to optimize trapping stability, trapping time, shear stress, and sample metabolism. Herein, the effects of hydrodynamics and diffusion-reaction on tissue viability and device operation are investigated using analytical and finite element methods with systematic parametric sweeps over independent design variables chosen to correspond to the four design degrees of freedom. Combining different results, we show that, for a spherical tissue of diameterd < 500 μm, the simplest, closest to optimal trap shape is a cube of dimensionsw equal to twice the tissue diameter:w = 2d. Furthermore, to sustain tissues without perfusion, available medium volume per trap needs to be 100× the tissue volume to ensure optimal metabolism for at least 24 hours.
Theoretical and computational validation of the Kuhn barrier friction mechanism in unfolded proteins
Authors: Avdoshenko Stanislav M. , Das Atanu , Satija Rohit , Papoian Garegin A. , Makarov Dmitrii E.
Published: March 2017

A long time ago, Kuhn predicted that long polymers should approach a limit where their global motion is controlled by solvent friction alone, with ruggedness of their energy landscapes having no consequences for their dynamics. In contrast, internal friction effects are important for polymers of modest length. Internal friction in proteins, in particular, affects how fast they fold or find their binding targets and, as such, has attracted much recent attention. Here we explore the molecular origins of internal friction in unfolded proteins using atomistic simulations, coarse-grained models and analytic theory. We show that the characteristic internal friction timescale is directly proportional to the timescale of hindered dihedral rotations within the polypeptide chain, with a proportionality coefficient b that is independent of the chain length. Such chain length independence of b provides experimentally testable evidence that internal friction arises from concerted, crankshaft-like dihedral rearrangements. In accord with phenomenological models of internal friction, we find the global reconfiguration timescale of a polypeptide to be the sum of solvent friction and internal friction timescales. At the same time, the time evolution of inter-monomer distances within polypeptides deviates both from the predictions of those models and from a simple, one-dimensional diffusion model.
A Microplate Reader-Based System for Visualizing Transcriptional Activity During in vivo Microbial Interactions in Space and Time
Authors: Hennessy Rosanna C. , Stougaard Peter , Olsson Stefan
Published: March 2017

Here, we report the development of a microplate reader-based system for visualizing gene expression dynamics in living bacterial cells in response to a fungus in space and real-time. A bacterium expressing the red fluorescent protein mCherry fused to the promoter region of a regulator gene nunF indicating activation of an antifungal secondary metabolite gene cluster was used as a reporter system. Time-lapse image recordings of the reporter red signal and a green signal from fluorescent metabolites combined with microbial growth measurements showed that nunF-regulated gene transcription is switched on when the bacterium enters the deceleration growth phase and upon physical encounter with fungal hyphae. This novel technique enables real-time live imaging of samples by time-series multi-channel automatic recordings using a microplate reader as both an incubator and image recorder of general use to researchers. The technique can aid in deciding when to destructively sample for other methods e.g. transcriptomics and mass spectrometry imaging to study gene expression and metabolites exchanged during the interaction.
In-Situ GISAXS Study of Supramolecular Nanofibers having Ultrafast Humidity Sensitivity
Authors: Bhattacharyya Arpan , Sanyal Milan K. , Mogera Umesha , George Subi J. , Mukhopadhyay Mrinmay K. , Maiti Santanu , Kulkarni Giridhar U.
Published: March 2017

Self assembled nanofibers derived from donor-acceptor (D-A) pair of dodecyl methyl viologen (DMV) and potassium salt of coronene tetracarboxylate (CS) is an excellent material for the development of organic electronic devices particularly for ultrafast response to relative humidity (RH). Here we have presented the results of in-situ grazing incidence small angle x-ray scattering (GISAXS) measurements to understand aridity dependent self reorganization of the nanofibers. The instantaneous changes in the organization of the nanofibers was monitored with different equilibrium RH conditions. Additionally formation of nanofibers during drying was studied by GISAXS technique – the results show two distinct stages of structural arrangements, first the formation of a lamellar mesophase and then, the evolution of a distorted hexagonal lattice. The RH dependent GISAXS results revealed a high degree of swelling in the lattice of the micelles and reduction in the distortion of the hexagonal structure with increase in RH. In high RH condition, the nanofibers show elliptical distortion but could not break into lamellar phase as observed during formation through drying. This observed structural deformation gives insight into nanoscopic structural changes of the micelles with change in RH around it and in turn explains ultrafast sensitivity in its conductivity for RH variation.
Night and day variations of sleep in patients with disorders of consciousness
Authors: Wislowska Malgorzata , del Giudice Renata , Lechinger Julia , Wielek Tomasz , Heib Dominik P. J. , Pitiot Alain , Pichler Gerald , Michitsch Gabriele , Donis Johann , Schabus Manuel
Published: March 2017

Brain injuries substantially change the entire landscape of oscillatory dynamics and render detection of typical sleep patterns difficult. Yet, sleep is characterized not only by specific EEG waveforms, but also by its circadian organization. In the present study we investigated whether brain dynamics of patients with disorders of consciousness systematically change between day and night. We recorded ~24 h EEG at the bedside of 18 patients diagnosed to be vigilant but unaware (Unresponsive Wakefulness Syndrome) and 17 patients revealing signs of fluctuating consciousness (Minimally Conscious State). The day-to-night changes in (i) spectral power, (ii) sleep-specific oscillatory patterns and (iii) signal complexity were analyzed and compared to 26 healthy control subjects. Surprisingly, the prevalence of sleep spindles and slow waves did not systematically vary between day and night in patients, whereas day-night changes in EEG power spectra and signal complexity were revealed in minimally conscious but not unaware patients.
Egg antigen p40 of Schistosoma japonicum promotes senescence in activated hepatic stellate cells via SKP2/P27 signaling pathway
Authors: Xu Tianhua , Chen Jinling , Zhu Dandan , Chen Liuting , Wang Jianxin , Sun Xiaolei , Hu Bin , Duan Yinong
Published: March 2017

Schistosomiasis is characterized by egg deposition, granulomatous inflammatory reaction and then subsequent hepatic fibrosis formation. Activated HSCs are regarded as the main effector cells in the progression of liver fibrosis and induction of senescence in hepatic stellate cells (HSCs) is vital to the reversion of hepatic fibrosis. Our previous work has showed that S. japonicum egg antigen p40 (Sjp40) could promote HSCs senescence via a STAT3/p53/p21 mechanism. In this paper, the major aim was to explore whether there are other signaling pathways in the process of Sjp40-induced HSCs aging and the underlying effect of SKP2/P27 signal pathway in this procedure. We observed the Sjp40-induced decrease of α-SMA and the senescence of LX-2 cells, and Sjp40 could upregulate P27 and downregulate the protein level of SKP2. The senescence induced by Sjp40 might be reversed in LX-2 cells that treated with P27-specific siRNA or with SKP2-special over-expression plasmid. In addition, we also demonstrated that the decreased expression of P-Rb and α-SMA induced by Sjp40 were partly restored by SKP2-overexpression. These data suggest that Sjp40 might inhibit HSCs activation by promoting cellular senescence via SKP2/P27 signaling pathway, which put forward novel mechanism in the treatment of liver fibrosis.
PEGylated insulin-like growth factor-I affords protection and facilitates recovery of lost functions post-focal ischemia
Authors: Parker Kim , Berretta Antonio , Saenger Stefanie , Sivaramakrishnan Manaswini , Shirley Simon A. , Metzger Friedrich , Clarkson Andrew N.
Published: March 2017

Insulin-like growth factor-I (IGF-I) is involved in the maturation and maintenance of neurons, and impaired IGF-I signaling has been shown to play a role in various neurological diseases including stroke. The aim of the present study was to investigate the efficacy of an optimized IGF-I variant by adding a 40 kDa polyethylene glycol (PEG) chain to IGF-I to form PEG-IGF-I. We show that PEG-IGF-I has a slower clearance which allows for twice-weekly dosing to maintain steady-state serum levels in mice. Using a photothrombotic model of focal stroke, dosing from 3 hrs post-stroke dose-dependently (0.3–1 mg/kg) decreases the volume of infarction and improves motor behavioural function in both young 3-month and aged 22–24 month old mice. Further, PEG-IGF-I treatment increases GFAP expression when given early (3 hrs post-stroke), increases Synaptophysin expression and increases neurogenesis in young and aged. Finally, neurons (P5–6) cultured in vitro on reactive astrocytes in the presence of PEG-IGF-I showed an increase in neurite length, indicating that PEG-IGF-I can aid in sprouting of new connections. This data suggests a modulatory role of IGF-I in both protective and regenerative processes, and indicates that therapeutic approaches using PEG-IGF-I should be given early and where the endogenous regenerative potential is still high.
Prognostic value of CA20, a score based on centrosome amplification-associated genes, in breast tumors
Authors: Ogden Angela , Rida Padmashree C. G. , Aneja Ritu
Published: March 2017

Centrosome amplification (CA) is a hallmark of cancer, observable in ≥75% of breast tumors. CA drives aggressive cellular phenotypes such as chromosomal instability (CIN) and invasiveness. Thus, assessment of CA may offer insights into the prognosis of breast cancer and identify patients who might benefit from centrosome declustering agents. However, it remains unclear whether CA is correlated with clinical outcomes after adjusting for confounding factors. To gain insights, we developed a signature, “CA20”, comprising centrosome structural genes and genes whose dysregulation is implicated in inducing CA. We found that CA20 was a significant independent predictor of worse survival in two large independent datasets after adjusting for potentially confounding factors. In multivariable analyses including both CA20 and CIN25 (a gene expression-based score that correlates with aneuploidy and has prognostic value in many types of cancer), only CA20 was significant, suggesting CA20 captures the risk-predictive information of CIN25 and offers information beyond it. CA20 correlated strongly with CIN25, so a high CA20 score may reflect tumors with high CIN and potentially other aggressive features that may require more aggressive treatment. Finally, we identified processes and pathways differing between CA20-low and high groups that may be valuable therapeutic targets.
Photosensitization of TiO2 nanofibers by Ag2S with the synergistic effect of excess surface Ti3+ states for enhanced photocatalytic activity under simulated sunlight
Authors: Ghafoor Samina , Ata Sadia , Mahmood Nasir , Arshad Salman Noshear
Published: March 2017

TiO2 nanofibers, with mean diameter ~200 nm, were fabricated by electrospinning and successfully photosensitized with low bandgap Ag2S nanoparticles of 11, 17, 23 and 40 nm mean sizes, with corresponding loading of 4, 10, 18 and 29 wt.% Ag2S, respectively. 17 nm Ag2S@TiO2 nanofibers exhibited optimal activity in the photodegradation of methylene blue under simulated sunlight with pseudo-first order rate constant of 0.019 min−1 compared to 0.009 min−1 for pure TiO2 nanofibers. In spite of greater visible-light absorption and reduced bandgap, larger than 17 nm Ag2S nanoparticles exhibited sluggish photodegradation kinetics probably due to less photo-induced carriers generation in TiO2 and reduced electron injection rates from the larger sized Ag2S into TiO2. Furthermore, a UV-O3 surface treatment induced excess Ti3+ surface states and oxygen vacancies which synergistically enhanced the photodegradation rate constant to 0.030 min−1 for 17 nm Ag2S@TiO2 sample which is ~70% better than the previously reported for Ag2S/TiO2 hierarchical spheres. This was attributed to the efficient charge separation and transfer driven by increased visible-light absorption, bandgap narrowing and reduced electron-hole recombination rates. The present study demonstrate the potential utilization of Ag2S@TiO2 nanofibers in filtration membranes for removal of organic pollutants from wastewater.
Blue organic light-emitting diodes realizing external quantum efficiency over 25% using thermally activated delayed fluorescence emitters
Authors: Miwa Takuya , Kubo Shosei , Shizu Katsuyuki , Komino Takeshi , Adachi Chihaya , Kaji Hironori
Published: March 2017

Improving the performance of blue organic light-emitting diodes (OLEDs) is needed for full-colour flat-panel displays and solid-state lighting sources. The use of thermally activated delayed fluorescence (TADF) is a promising approach to efficient blue electroluminescence. However, the difficulty of developing efficient blue TADF emitters lies in finding a molecular structure that simultaneously incorporates (i) a small energy difference between the lowest excited singlet state (S1) and the lowest triplet state (T1), ΔEST, (ii) a large oscillator strength, f, between S1 and the ground state (S0), and (iii) S1 energy sufficiently high for blue emission. In this study, we develop TADF emitters named CCX-I and CCX-II satisfying the above requirements. They show blue photoluminescence and high triplet-to-singlet up-conversion yield. In addition, their transition dipole moments are horizontally oriented, resulting in further increase of their electroluminescence efficiency. Using CCX-II as an emitting dopant, we achieve a blue OLED showing a high external quantum efficiency of 25.9%, which is one of the highest EQEs in blue OLEDs reported previously.
Efficient Generation of diRNAs Requires Components in the Posttranscriptional Gene Silencing Pathway
Authors: Miki Daisuke , Zhu Peiying , Zhang Wencan , Mao Yanfei , Feng Zhengyan , Huang Huan , Zhang Hui , Li Yanqiang , Liu Renyi , Zhang Huiming , Qi Yijun , Zhu Jian-Kang
Published: March 2017

It has been reported that double-stranded break (DSB)-induced small RNAs (diRNAs) are generated via the RNA-directed DNA methylation pathway and function in DSB repair in Arabidposis. However, important questions remain regarding the biogenesis and function of diRNAs. Here, we used CRISPR/Cas9- or TALEN-triggered DSBs to characterize diRNAs in Arabidopsis and rice. We found that 21-nt diRNAs were generated from a 35S promoter::GU-US reporter transgene targeted by CRISPR/Cas9. Unexpectedly, Pol II transcription of the transgene was required for efficient diRNA production and the level of diRNA accumulation correlated with the expression level of the transgene. diRNAs were not detected from CRISPR/Cas9- or TALEN-induced DSBs within the examined endogenous genes in Arabidopsis or rice. We also found that DCL4 and RDR6 that are known to be involved in posttranscriptional gene silencing were required to generate diRNAs. Our results suggest that DSBs are necessary but not sufficient for efficient diRNA generation and a high level of diRNAs is not necessary for DSB repair.
Discriminating between natural and anthropogenic earthquakes: insights from the Emilia Romagna (Italy) 2012 seismic sequence
Authors: Albano Matteo , Barba Salvatore , Tarabusi Gabriele , Saroli Michele , Stramondo Salvatore
Published: March 2017

The potential for oilfield activities to trigger earthquakes in seismogenic areas has been hotly debated. Our model compares the stress changes from remote water injection and a natural earthquake, both of which occurred in northern Italy in recent years, and their potential effects on a nearby Mw 5.9 earthquake that occurred in 2012. First, we calculate the Coulomb stress from 20 years of fluid injection in a nearby oilfield by using a poroelastic model. Then, we compute the stress changes for a 2011 Mw 4.5 earthquake that occurred close to the area of the 2012 mainshock. We found that anthropogenic activities produced an effect that was less than 10% of that generated by the Mw 4.5 earthquake. Therefore, the 2012 earthquake was likely associated with a natural stress increase. The probability of triggering depends on the magnitude of recent earthquakes, the amount of injected water, the distance from an event, and the proximity to the failure of the activated fault. Determining changes that are associated with seismic hazards requires poroelastic area-specific models that include both tectonic and anthropogenic activities. This comprehensive approach is particularly important when assessing the risk of triggered seismicity near densely populated areas.
The long non-coding RNA LINC01013 enhances invasion of human anaplastic large-cell lymphoma
Authors: Chung I-Hsiao , Lu Pei-Hsuan , Lin Yang-Hsiang , Tsai Ming-Ming , Lin Yun-Wen , Yeh Chau-Ting , Lin Kwang-Huei
Published: March 2017

Anaplastic large-cell lymphoma (ALCL) is a rare type of highly malignant, non-Hodgkin lymphoma (NHL). Currently, only studies on the chimeric oncogene NPM-ALK have reported a link to ALCL progression. However, the specific molecular mechanisms underlying the invasion of ALCL are still unclear. Here, we sought to investigate differentially expressed, long non-coding RNAs (lncRNAs) in ALCL and their potential biological function. Our microarray analyses revealed that LINC01013, a novel non-coding RNA gene, was highly expressed in clinical specimens of ALCL and was significantly upregulated in invasive ALCL cell lines. Knockdown of LINC01013 suppressed tumor cell invasion; conversely, its overexpression enhanced tumor cell invasion. LINC01013-induced invasion was mediated by activation of the epithelial-to-mesenchymal transition (EMT)-associated proteins, snail and fibronectin. Specifically, LINC01013 induced snail, resulting in activation of fibronectin and enhanced ALCL cell invasion. Collectively, these findings support a potential role for LINC01013 in cancer cell invasion through the snail-fibronectin activation cascade and suggest that LINC01013 could potentially be utilized as a metastasis marker in ALCL.
A permanent host shift of rabies virus from Chiroptera to Carnivora associated with recombination
Authors: Ding Nai-Zheng , Xu Dong-Shuai , Sun Yuan-Yuan , He Hong-Bin , He Cheng-Qiang
Published: March 2017

Bat virus host shifts can result in the spread of diseases with significant effects. The rabies virus (RABV) is able to infect almost all mammals and is therefore a useful model for the study of host shift mechanisms. Carnivore RABVs originated from two historical host shifts from bat viruses. To reveal the genetic pathways by which bat RABVs changed their host tropism from bats to carnivores, we investigated the second permanent bat-to-carnivore shift resulting in two carnivore variants, known as raccoon RABV (RRV) and south-central skunk RABV (SCSKV). We found that their glycoprotein (G) genes are the result of recombination between an American bat virus and a carnivore virus. This recombination allowed the bat RABV to acquire the head of the G-protein ectodomain of the carnivore virus. This region is involved in receptor recognition and binding, response to changes in the pH microenvironment, trimerization of G proteins, and cell-to-cell transmission during the viral infection. Therefore, this recombination event may have significantly improved the variant’s adaptability to carnivores, altering its host tropism and thus leading to large-scale epidemics in striped skunk and raccoon.
The Role of Angiotensin II in Glomerular Volume Dynamics and Podocyte Calcium Handling
Authors: Ilatovskaya Daria V. , Palygin Oleg , Levchenko Vladislav , Endres Bradley T. , Staruschenko Alexander
Published: March 2017

Podocytes are becoming a primary focus of research efforts due to their association with progressive glomeruli damage in disease states. Loss of podocytes can occur as a result of excessive intracellular calcium influx, and we have previously shown that angiotensin II (Ang II) via canonical transient receptor potential 6 (TRPC6) channels caused increased intracellular Ca2+ flux in podocytes. We showed here with patch-clamp electrophysiology that Ang II activates TRPC channels; then using confocal calcium imaging we demonstrated that Ang II–dependent stimulation of Ca2+ influx in the podocytes is precluded by blocking either AT1 or AT2 receptors (ATRs). Application of Ang(1–7) had no effect on intracellular calcium. Ang II-induced calcium flux was decreased upon inhibition of TRPC channels with SAR7334, SKF 96365, clemizole hydrochloride and La3+, but not ML204. Using a novel 3D whole-glomerulus imaging ex vivo assay, we revealed the involvement of both ATRs in controlling glomerular permeability; additionally, using specific inhibitors and activators of TRPC6, we showed that these channels are implicated in the regulation of glomerular volume dynamics. Therefore, we provide evidence demonstrating the critical role of Ang II/TRPC6 axis in the control of glomeruli function, which is likely important for the development of glomerular diseases.
Increased dosage of AOX1 promoter-regulated expression cassettes leads to transcription attenuation of the methanol metabolism in Pichia pastoris
Authors: Cámara Elena , Landes Nils , Albiol Joan , Gasser Brigitte , Mattanovich Diethard , Ferrer Pau
Published: March 2017

The methanol-regulated alcohol oxidase promoter (PAOX1) of Pichia pastoris is one of the strongest promoters for heterologous gene expression in this methylotrophic yeast. Although increasing gene dosage is one of the most common strategies to increase recombinant protein productivities, the increase of gene dosage of Rhizopus oryzae lipase (ROL) in P. pastoris has been previously shown to reduce cell growth, lipase production and substrate consumption in high-copy strains. To better assess that physiological response, transcriptomics analysis was performed of a subset of strains with 1 to 15 ROL copies. The macroscopic physiological parameters confirm that growth yield and carbon uptake rate are gene dosage dependent, and were supported by the transcriptomic data, showing the impact of increased dosage of AOX1 promoter-regulated expression cassettes on P. pastoris physiology under steady methanolic growth conditions. Remarkably, increased number of cassettes led to transcription attenuation of the methanol metabolism and peroxisome biogenesis in P. pastoris, concomitant with reduced secretion levels of the heterologous product. Moreover, our data also point to a block in ROL mRNA translation in the higher ROL-copies constructs, while the low productivities of multi-copy strains under steady growth conditions do not appear to be directly related to UPR and ERAD induction.
Intrinsic optimization using stochastic nanomagnets
Authors: Sutton Brian , Camsari Kerem Yunus , Behin-Aein Behtash , Datta Supriyo
Published: March 2017

This paper draws attention to a hardware system which can be engineered so that its intrinsic physics is described by the generalized Ising model and can encode the solution to many important NP-hard problems as its ground state. The basic constituents are stochastic nanomagnets which switch randomly between the ±1 Ising states and can be monitored continuously with standard electronics. Their mutual interactions can be short or long range, and their strengths can be reconfigured as needed to solve specific problems and to anneal the system at room temperature. The natural laws of statistical mechanics guide the network of stochastic nanomagnets at GHz speeds through the collective states with an emphasis on the low energy states that represent optimal solutions. As proof-of-concept, we present simulation results for standard NP-complete examples including a 16-city traveling salesman problem using experimentally benchmarked models for spin-transfer torque driven stochastic nanomagnets.
Cardiac repair in a mouse model of acute myocardial infarction with trophoblast stem cells
Authors: Li Guannan , Chen Jianzhou , Zhang Xinlin , He Guixin , Tan Wei , Wu Han , Li Ran , Chen Yuhan , Gu Rong , Xie Jun , Xu Biao
Published: March 2017

Various stem cells have been explored for the purpose of cardiac repair. However, any individual stem cell population has not been considered as the ideal source. Recently, trophoblast stem cells (TSCs), a newly described stem cell type, have demonstrated extensive plasticity. The present study evaluated the therapeutic effect of TSCs transplantation for heart regeneration in a mouse model of myocardial infarction (MI) and made a direct comparison with the most commonly used mesenchymal stem cells (MSCs). Transplantation of TSCs and MSCs led to a remarkably improved cardiac function in contrast with the PBS control, but only the TSCs exhibited the potential of differentiation into cardiomyocytes in vivo. In addition, a significantly high proliferation level of both transplanted stem cells and resident cardiomyocytes was observed in the TSCs group. These findings primary revealed the therapeutic potential of TSCs in transplantation therapy for MI.
Down regulation of ADAM33 as a Predictive Biomarker of Aggressive Breast Cancer
Authors: Manica Graciele C. M. , Ribeiro Caroline F. , Oliveira Marco A. S. de , Pereira Isabela T. , Chequin Andressa , Ramos Edneia A. S. , Klassen Liliane M. B. , Sebastião Ana Paula M. , Alvarenga Larissa M. , Zanata Silvio M. , Noronha Lucia De , Rabinovich Iris , Costa Fabricio F. , Souza Emanuel M. , Klassen Giseli
Published: March 2017

Breast cancer is a heterogeneous disease with differences in its clinical, molecular and biological features. Traditionally, immunohistochemical markers together with clinicopathologic parameters are used to classify breast cancer and to predict disease outcome. Triple-negative breast cancer (TNBC) is a particular type of breast cancer that is defined by a lack of expression of hormonal receptors and the HER2 gene. Most cases of TNBC also have a basal-like phenotype (BLBC) with expression of cytokeratin 5/6 and/or EGFR. A basal marker alone is insufficient for a better understanding of the tumor biology of TNBC. In that regard, the ADAM33 gene is silenced by DNA hypermethylation in breast cancer, which suggests that ADAM33 might be useful as a molecular marker. In the present study, we have produced monoclonal antibodies against the ADAM33 protein and have investigated the role of ADAM33 protein in breast cancer. We used 212 breast tumor samples and lower levels of ADAM33 were correlated with TNBC and basal-like markers. A lower level of ADAM33 was also correlated with shorter overall survival and metastasis-free survival and was considered an independent prognostic factor suggesting that ADAM33 is a novel molecular biomarker of TNBC and BLBC that might be useful as a prognostic factor.
The age-associated loss of ischemic preconditioning in the kidney is accompanied by mitochondrial dysfunction, increased protein acetylation and decreased autophagy
Authors: Jankauskas Stanislovas S. , Pevzner Irina B. , Andrianova Nadezda V. , Zorova Ljubava D. , Popkov Vasily A. , Silachev Denis N. , Kolosova Nataliya G. , Plotnikov Egor Y. , Zorov Dmitry B.
Published: March 2017

In young rats, ischemic preconditioning (IPC), which consists of 4 cycles of ischemia and reperfusion alleviated kidney injury caused by 40-min ischemia. However,old rats lost their ability to protect the ischemic kidney by IPC. A similar aged phenotype was demonstrated in 6-month-old OXYS rats having signs of premature aging. In the kidney of old and OXYS rats, the levels of acetylated nuclear proteins were higher than in young rats, however, unlike in young rats, acetylation levels in old and OXYS rats were further increased after IPC. In contrast to Wistar rats, age-matched OXYS demonstrated no increase in lysosome abundance and LC3 content in the kidney after ischemia/reperfusion. The kidney LC3 levels were also lower in OXYS, even under basal conditions, and mitochondrial PINK1 and ubiquitin levels were higher, suggesting impaired mitophagy. The kidney mitochondria from old rats contained a population with diminished membrane potential and this fraction was expanded by IPC. Apparently, oxidative changes with aging result in the appearance of malfunctioning renal mitochondria due to a low efficiency of autophagy. Elevated protein acetylation might be a hallmark of aging which is associated with a decreased autophagy, accumulation of dysfunctional mitochondria, and loss of protection against ischemia by IPC.