bluuebunny/crossref_metadata_2025 huggingface dataset:
Hegel, Deleuze/Guattari and Political Immanence: The Sons of Rousseau
Authors: Hristov George
Published: July 2018

In the article I argue that Hegel and Deleuze/Guattari construct two distinct political paths toward immanence. Both of these paths have as their starting point Rousseau’s bourgeois. I show that both thinkers follow Rousseau in his attempt to construct political immanence and abandon the position of private man. However, in doing so they move in opposite directions. Hegel seeks to convert the bourgeois into the citizen, with the intention of reformulating the immanence of state-life presented in the The Social Contract by extending mutual recognition a distinct space in the form of civil society. In contrast Deleuze/Guattari move in the direction of becoming-animal along the lines of the Discourse on Inequality, by reformulating the relationship between life and society. At the same time, I argue that the overcoming of the problems that Hegel and Deleuze/Guattari identified in Rousseau introduces new ones and that the dangers inherent in the project of immanence cannot disappear.
Fully resolved measurements of turbulent boundary layer flows up to
Authors: Samie M. , Marusic I. , Hutchins N. , Fu M. K. , Fan Y. , Hultmark M. , Smits A. J.
Published: July 2018

Fully resolved measurements of turbulent boundary layers are reported for the Reynolds number range $Re_{\unicode[STIX]{x1D70F}}=6000{-}20\,000$. Despite several decades of research in wall-bounded turbulence there is still controversy over the behaviour of streamwise turbulence intensities near the wall, especially at high Reynolds numbers. Much of it stems from the uncertainty in measurement due to finite spatial resolution. Conventional hot-wire anemometry is limited for high Reynolds number measurements due to limited spatial resolution issues that cause attenuation in the streamwise turbulence intensity profile near the wall. To address this issue we use the nano-scale thermal anemometry probe (NSTAP), developed at Princeton University to conduct velocity measurements in the high Reynolds number boundary layer facility at the University of Melbourne. The NSTAP has a sensing length almost one order of magnitude smaller than conventional hot-wires. This enables us to acquire fully resolved velocity measurements of turbulent boundary layers up to $Re_{\unicode[STIX]{x1D70F}}=20\,000$. Results show that in the near-wall region, the viscous-scaled streamwise turbulence intensity grows with $Re_{\unicode[STIX]{x1D70F}}$ in the Reynolds number range of the experiments. A second outer peak in the streamwise turbulence intensity is also shown to emerge at the highest Reynolds numbers. Moreover, the energy spectra in the near-wall region show excellent inner scaling over the small to moderate wavelength range, followed by a large-scale influence that increases with Reynolds number. Outer scaling in the outer region is found to collapse the energy spectra over high wavelengths across various Reynolds numbers.
REVISION OF MEZIA (MALPIGHIACEAE)
Authors: Anderson C.
Published: July 2018

The Neotropical genus Mezia (Malpighiaceae) comprises 15 species of lianas (except M. huberi W.R.Anderson, a shrub or small tree). All have multibranched, densely brown-sericeous inflorescences with the ultimate unit a 4-flowered umbel of bilaterally symmetrical flowers. The distinctive pair of large cymbiform bracteoles subtends a rudimentary pedicel and encloses the floral bud. The flowers contain elongate sepals, the lateral four biglandular, yellow petals, the posterior often splotched with red, a heteromorphic androecium, and a tricarpellate gynoecium. The three styles are all free; the posterior pair is lyrate in five species but erect in the others. The samaras have an orbicular to oblate lateral wing and a much smaller dorsal wing; in most species, additional winglets and/or crests are present between the lateral and dorsal wings. Only Mezia mariposa W.R.Anderson has butterfly-shaped samaras lacking additional ornamentation. Four new species are proposed: Mezia andersonii C.E.Anderson, M. bahiana C.E.Anderson, M. fanshawei C.E.Anderson and M. sericea C.E.Anderson. One variety is elevated to species level and provided with a new name, Mezia peruviana C.E.Anderson; a lectotype is chosen for Diplopterys involuta var. ovata Nied. Full descriptions and synonymies are provided, as well as a distribution map. All species are illustrated.
The ethics of negative emissions
Authors: Lenzi Dominic
Published: July 2018

Non-technical abstract

Limiting dangerous climate change is widely believed to require negative emissions. This prospect has sparked concerns about whether negative emissions could be scaled up quickly enough, along with concerns about their likely ethical costs. Building upon scenario modelling, this paper examines ethical concerns with negative emissions via the comparison of three alternate climate futures. This paper shows that the severity of concerns depends upon implementation conditions, and especially the extent of deferred mitigation. Negative emissions can be a valuable means of limiting dangerous climate change, or an unjust gamble against the future.
Mapping Risk from Genes to Behavior: The Enduring and Evolving Influence of Irving Gottesman's Endophenotype Concept
Authors: Dick Danielle M.
Published: July 2018

One of Irving I. Gottesman's many contributions to behavior genetics, and part of his enduring legacy, was his introduction of the term ‘endophenotype’ to the field of psychiatry. Gottesman argued that focusing on endophenotypes, rather than complex heterogeneous clinical diagnoses, could help elucidate disease etiology. Although a different strategy for gene identification ultimately proved successful (that of amassing extremely large sample sizes in order to overcome the ‘noise’ of heterogeneity and have sufficient power to find genes of very small effect), the endophenotype concept continues to make a meaningful contribution to the field. The endophenotype concept forced the field to move beyond a simple disease model of finding genes ‘for’ psychiatric outcomes, and reminded us that genes are quite distal from complex behavioral outcomes and disorders. Endophenotypes called our attention to the steps along that pathway. In that process, the concept of endophenotypes evolved and expanded to include discussion of the role that other intermediary traits and psychological processes play in the development and genetic etiology of psychiatric and substance use disorders. As large-scale consortia continues to identify genes and generate genome-wide polygenic scores that are associated with behavioral outcomes, the next important step will be to characterize the pathways and mechanisms by which genetic risk unfolds. This essential step of mapping risk from genes to behavior is an evolution that follows naturally from the endophenotype concept, and could ultimately translate into improved prevention and intervention for individuals who are pre-disposed to mental health challenges.
Interhemispheric Survey of Polar Cap Aurora
Authors: Reidy J. A. , Fear R. C. , Whiter D. K. , Lanchester B. , Kavanagh A. J. , Milan S. E. , Carter J. A. , Paxton L. J. , Zhang Y.
Published: July 2018

This study investigates the interhemispheric nature of polar cap auroras via ultraviolet imaging, combined with particle data, to determine whether they occur on open or closed field lines. Data from the SSUSI (Special Sensor Ultraviolet Spectrographic Imager) instrument on board the DMSP (Defence Meteorological Satellite Program) spacecraft are examined. The DMSP spacecraft are in 90‐min orbits; hence, images of each hemisphere are separated by 45 min providing a good opportunity for interhemispheric study. 21 polar cap arc (PCA) events are recorded in December 2015 which have particle data from the SSJ/4 particle spectrometer associated with an arc in at least one hemisphere. Nine events are found to contain "arcs" consistent with a closed field line mechanism, that is, arcs associated with an ion signature present in both hemispheres. Six events contained arcs that were consistent with an "open field line" mechanism, that is, they were associated with electron‐only precipitation. Events containing arcs that were not consistent with either of these expectations are also explored, including an example of a "non‐conjugate" theta aurora and an interesting example of auroral morphology similar to a PCA which is associated with a geomagnetic storm. Seasonal effects are also investigated through a statistical analysis of PCAs over 4 months in 2015. It is found that PCAs are visible in the SSUSI data at least 20% of the time and that it is likely some are missed due to the spacecraft field of view and poor sensitivity in the summer hemisphere due to increased solar illumination.
Under What Conditions Can We Trust Retrieved Cloud Drop Concentrations in Broken Marine Stratocumulus?
Authors: Zhu Yannian , Rosenfeld Daniel , Li Zhanqing
Published: July 2018

In this study, we show how to obtain more reliable satellite‐retrieved cloud drop number concentrations (Nd) from Moderate Resolution Imaging Spectroradiometer (MODIS) standard cloud products. Nd is important as a fundamental cloud property that determines cloud albedo, precipitation‐forming processes, cloud longevity, and fractional cover, all of which determine cloud radiative effects. Nd is determined by cloud base aerosols and updrafts. Satellite retrievals of Nd for marine stratocumulus clouds are performed based on the assumption of a nearly adiabatic cloud column. The retrievals, however, are fraught with problems that cause large biases (e.g., the retrieved Nd for partially filled cloudy pixels are less than one third of the retrieved Nd for the convective cores) and limit the usefulness of Nd, especially in broken cloud fields. The Nd of the brightest 10% of cloudy pixels are selected because the brightest clouds are the convective cores that most closely follow adiabatic parcels, a key assumption of our retrieval. It is shown that this criterion is representative of pixels that are also fully surrounded by cloudy pixels (Nd agreement within 5%).
Observations and Modeling of Increased Nitric Oxide in the Antarctic Polar Middle Atmosphere Associated With Geomagnetic Storm‐Driven Energetic Electron Precipitation
Authors: Newnham D. A. , Clilverd M. A. , Rodger C. J. , Hendrickx K. , Megner L. , Kavanagh A. J. , Seppälä A. , Verronen P. T. , Andersson M. E. , Marsh D. R. , Kovács T. , Feng W. , Plane J. M. C.
Published: July 2018

Nitric oxide (NO) produced in the polar middle and upper atmosphere by energetic particle precipitation depletes ozone in the mesosphere and, following vertical transport in the winter polar vortex, in the stratosphere. Medium‐energy electron (MEE) ionization by 30–1,000 keV electrons during geomagnetic storms may have a significant role in mesospheric NO production. However, questions remain about the relative importance of direct NO production by MEE at altitudes ~60–90 km versus indirect NO originating from auroral ionization above 90 km. We investigate potential drivers of NO variability in the southern‐hemisphere mesosphere and lower thermosphere during 2013–2014. Contrasting geomagnetic activity occurred during the two austral winters, with more numerous moderate storms in the 2013 winter. Ground‐based millimeter‐wave observations of NO from Halley, Antarctica, are compared with measurements by the Solar Occultation For Ice Experiment (SOFIE) spaceborne spectrometer. NO partial columns over the altitude range 65–140 km from the two observational data sets show large day‐to‐day variability and significant disagreement, with Halley values on average 49% higher than the corresponding SOFIE data. SOFIE NO number densities, zonally averaged over geomagnetic latitudes −59° to −65°, are up to 3 × 108/cm3higher in the winter of 2013 compared to 2014. Comparisons with a new version of the Whole Atmosphere Community Climate Model, which includes detailedD‐region ion chemistry (WACCM‐SIC) and MEE ionization rates, show that the model underestimates NO in the winter lower mesosphere whereas thermospheric abundances are too high. This indicates the need to further improve and verify WACCM‐SIC with respect to MEE ionization, thermospheric NO chemistry, and vertical transport.
Reservoir Imaging Using Ambient Noise Correlation From a Dense Seismic Network
Authors: Lehujeur M. , Vergne J. , Schmittbuhl J. , Zigone D. , Le Chenadec A. ,   EstOF Team
Published: July 2018

In September 2014, a dense temporary seismic network (EstOF) including 288 single‐component geophones was deployed during 1 month in the Outre‐Forêt region of the Upper Rhine Graben (France), where two deep geothermal projects (Soultz‐sous‐Forêts and Rittershoffen) are currently in operation. We apply ambient seismic noise correlation to estimate the empirical Green's function of the medium between the ~41,200 station pairs in the network. The noise correlation functions obtained are comparable to those from previous studies based on the sparse long‐term networks settled in the area mostly to monitor the induced seismic activity. However, the dense spatial coverage of the EstOF network improves our ability to identify the main phases of the Green's function. Both the fundamental mode and the first overtone of the Rayleigh waves are identified between most station pairs. P waves are also evidenced. We analyze the statistical distribution of the Rayleigh wave group velocity between station pairs as a function of the period (between 0.8 and 5 s), the station pair orientation, the distance over wavelength ratio and the signal‐to‐noise ratio. From these observations, we build a high‐resolution three‐dimensional S wave velocity model of the upper crust (down to 3 km deep) around the regional deep geothermal reservoirs. This model is consistent with local geological structures but also evidences nonlithological variations, particularly at depth in the basement. These variations are interpreted as large‐scale temperature anomalies related to deep hydrothermal circulation.
Sediment Dynamics in Wind Wave‐Dominated Shallow‐Water Environments
Authors: Nelson K. S. , Fringer O. B.
Published: July 2018

Sediment dynamics driven by waves and currents in shallow‐water estuarine environments impacts many physical and biological processes and is important to the estuary‐wide sediment budget. Observational restrictions have limited our ability to understand the physics governing sediment entrainment and mixing in these environments. To this end, we use direct numerical simulation to simulate sediment transport processes in shallow, combined wave‐ and current‐driven flows. Simulations are run with depth‐averaged currents ranging from 0 to 9 cm/s, while wave conditions are held constant with a bottom orbital velocity and period of 10 cm/s and 3 s, respectively. Our results indicated that for wave‐dominated conditions, waves reduce vertical momentum fluxes and the associated bottom drag, thereby accelerating mean currents. Conversely, currents do not significantly affect the wave velocity field. However, they increase the bed shear stress and change the timing and duration of sediment entrainment throughout the wave cycle. Counterintuitively, these effects lead to lower suspended sediment concentrations near the bed for a portion of the wave cycle. By analyzing sediment fluxes, waves are shown to drive near‐bed sediment dynamics while currents control vertical mixing above the buffer layer, where downward settling is predominantly balanced by the current‐generated vertical turbulent sediment flux. In the absence of currents, sediment concentrations are negligible above the wave boundary layer because mixing is weak. We show that the time‐ and phase‐averaged sediment concentration profiles for wave and current conditions resemble the theoretical Rouse profile derived for equilibrium conditions in statistically steady, unidirectional turbulent channel flow.
Comparison of Daytime Low‐Level Cloud Properties Derived From GOES and ARM SGP Measurements
Authors: McHardy Theodore M. , Dong Xiquan , Xi Baike , Thieman Mandana M. , Minnis Patrick , Palikonda Rabindra
Published: July 2018

Large‐scale satellite data are critical for both verifying and improving general circulation model parameterizations of clouds and radiation for climate prediction. For reliable application of satellite data sets in cloud processes and climate models, it is important to have a reasonable estimate of the errors in the derived cloud properties. The daytime single‐layered low‐level cloud properties retrieved by the Geostationary Operational Environmental Satellite system (GOES) are compared with ground‐based observations and retrievals over the Department of Energy Atmospheric Radiation Measurement (ARM) Southern Great Plains (SGP) Central Facility from June 1998 to December 2006. The GOES retrievals are made via the Visible‐Infrared Solar‐infrared Split‐window Technique. They are spatially averaged within a 0.15° × 0.15° box centered on the ARM SGP site, and the ARM surface observations are temporally averaged ±15 min around the GOES scans to produce collocated pairs. Comparisons are made for monthly means, diurnal means, and one‐to‐one GOES and ARM collocated pairs. GOES Teff is highly correlated with ARM Ttop cloud temperature, having an R2 value of 0.75, though GOES exhibits a cold bias. GOES‐retrieved τ and liquid water path have very good agreement with ARM retrievals with R2s of 0.45 and 0.47, while re (GOES), on average, is about 2 μm greater than ARM re. An examination of solar and viewing geometry has shown that GOES‐retrieved mean re and τ values are impacted by solar zenith angle and especially scattering angle, which is not unexpected and needs to be accounted for by users.
Merge and separation of NuA4 and SWR1 complexes control cell fate plasticity in Candida albicans
Authors: Wang Xiongjun , Zhu Wencheng , Chang Peng , Wu Hongyu , Liu Haoping , Chen Jiangye
Published: July 2018

Phenotypic plasticity is common in development. Candida albicans, a polymorphic fungal pathogen of humans, possesses the unique ability to achieve rapid and reversible cell fate between unicellular form (yeast) and multicellular form (hypha) in response to environmental cues. The NuA4 histone acetyltransferase activity and Hda1 histone deacetylase activity have been reported to be required for hyphal initiation and maintenance. However, how Hda1 and NuA4 regulate hyphal elongation is not clear. NuA4 histone acetyltransferase and SWR1 chromatin remodeling complexes are conserved from yeast to human, which may have merged together to form a larger TIP60 complex since the origin of metazoan. In this study, we show a dynamic merge and separation of NuA4 and SWR1 complexes in C. albicans. NuA4 and SWR1 merge together in yeast state and separate into two distinct complexes in hyphal state. We demonstrate that acetylation of Eaf1 K173 controls the interaction between the two complexes. The YEATS domain of Yaf9 in C. albicans can recognize an acetyl-lysine of the Eaf1 and mediate the Yaf9-Eaf1 interaction. The reversible acetylation and deacetylation of Eaf1 by Esa1 and Hda1 control the merge and separation of NuA4 and SWR1, and this regulation is triggered by Brg1 recruitment of Hda1 to chromatin in response nutritional signals that sustain hyphal elongation. We have also observed an orchestrated promoter association of Esa1, Hda1, Swr1, and H2A.Z during the reversible yeast–hyphae transitions. This is the first discovery of a regulated merge of the NuA4 and SWR1 complexes that controls cell fate determination and this regulation may be conserved in polymorphic fungi.
FABP4 as a key determinant of metastatic potential of ovarian cancer
Authors: Gharpure Kshipra M. , Pradeep Sunila , Sans Marta , Rupaimoole Rajesha , Ivan Cristina , Wu Sherry Y. , Bayraktar Emine , Nagaraja Archana S. , Mangala Lingegowda S. , Zhang Xinna , Haemmerle Monika , Hu Wei , Rodriguez-Aguayo Cristian , McGuire Michael , Mak Celia Sze Ling , Chen Xiuhui , Tran Michelle A. , Villar-Prados Alejandro , Pena Guillermo Armaiz , Kondetimmanahalli Ragini , Nini Ryan , Koppula Pranavi , Ram Prahlad , Liu Jinsong , Lopez-Berestein Gabriel , Baggerly Keith , S. Eberlin Livia , Sood Anil K.
Published: July 2018

The standard treatment for high-grade serous ovarian cancer is primary debulking surgery followed by chemotherapy. The extent of metastasis and invasive potential of lesions can influence the outcome of these primary surgeries. Here, we explored the underlying mechanisms that could increase metastatic potential in ovarian cancer. We discovered that FABP4 (fatty acid binding protein) can substantially increase the metastatic potential of cancer cells. We also found that miR-409-3p regulates FABP4 in ovarian cancer cells and that hypoxia decreases miR-409-3p levels. Treatment with DOPC nanoliposomes containing either miR-409-3p mimic or FABP4 siRNA inhibited tumor progression in mouse models. With RPPA and metabolite arrays, we found that FABP4 regulates pathways associated with metastasis and affects metabolic pathways in ovarian cancer cells. Collectively, these findings demonstrate that FABP4 is functionally responsible for aggressive patterns of disease that likely contribute to poor prognosis in ovarian cancer.
Non-hysteretic first-order phase transition with large latent heat and giant low-field magnetocaloric effect
Authors: Guillou F. , Pathak A. K. , Paudyal D. , Mudryk Y. , Wilhelm F. , Rogalev A. , Pecharsky V. K.
Published: July 2018

First-order magnetic transitions (FOMTs) with a large discontinuity in magnetization are highly sought in the development of advanced functional magnetic materials. Isosymmetric magnetoelastic FOMTs that do not perturb crystal symmetry are especially rare, and only a handful of material families, almost exclusively transition metal-based, are known to exhibit them. Yet, here we report a surprising isosymmetric FOMT in a rare-earth intermetallic, Eu2In. What makes this transition in Eu2In even more remarkable is that it is associated with a large latent heat and an exceptionally high magnetocaloric effect in low magnetic fields, but with tiny lattice discontinuities and negligible hysteresis. An active role of the Eu-5d and In-4p states and a rather unique electronic structure borne by In to Eu charge transfer, altogether result in an unusual exchange mechanism that both sets the transition in motion and unveils an approach toward developing specific magnetic functionalities ad libitum.
Exploring the performance of nanostructured reagents with organic-group-defined morphology in cross-coupling reaction
Authors: Kashin Alexey S. , Degtyareva Evgeniya S. , Eremin Dmitry B. , Ananikov Valentine P.
Published: July 2018

The great impact of the nanoscale organization of reactive species on their performance in chemical transformations creates the possibility of fine-tuning of reaction parameters by modulating the nano-level properties. This methodology is extensively applied for the catalysts development whereas nanostructured reactants represent the practically unexplored area. Here we report the palladium- and copper-catalyzed cross-coupling reaction involving nano-structured nickel thiolate particles as reagents. On the basis of experimental findings we propose the cooperative effect of nano-level and molecular-level properties on their reactivity. The high degree of ordering, small particles size, and electron donating properties of the substituents favor the product formation. Reactant particles evolution in the reaction is visualized directly by dynamic liquid-phase electron microscopy including recording of video movies. Mechanism of the reaction in liquid phase is established using on-line mass spectrometry measurements. Together the findings provide new opportunities for organic chemical transformations design and for mechanistic studies.
Glucose promotes cell growth by suppressing branched-chain amino acid degradation
Authors: Shao Dan , Villet Outi , Zhang Zhen , Choi Sung Won , Yan Jie , Ritterhoff Julia , Gu Haiwei , Djukovic Danijel , Christodoulou Danos , Kolwicz Stephen C. , Raftery Daniel , Tian Rong
Published: July 2018

Glucose and branched-chain amino acids (BCAAs) are essential nutrients and key determinants of cell growth and stress responses. High BCAA level inhibits glucose metabolism but reciprocal regulation of BCAA metabolism by glucose has not been demonstrated. Here we show that glucose suppresses BCAA catabolism in cardiomyocytes to promote hypertrophic response. High glucose inhibits CREB stimulated KLF15 transcription resulting in downregulation of enzymes in the BCAA catabolism pathway. Accumulation of BCAA through the glucose-KLF15-BCAA degradation axis is required for the activation of mTOR signaling during the hypertrophic growth of cardiomyocytes. Restoration of KLF15 prevents cardiac hypertrophy in response to pressure overload in wildtype mice but not in mutant mice deficient of BCAA degradation gene. Thus, regulation of KLF15 transcription by glucose is critical for the glucose-BCAA circuit which controls a cascade of obligatory metabolic responses previously unrecognized for cell growth.
The science of food security
Authors: Cole Martin Barry , Augustin Mary Ann , Robertson Michael John , Manners John Michael
Published: July 2018

We need to feed an estimated population in excess of 9 billion by 2050 with diminishing natural resources, whilst ensuring the health of people and the planet. Herein we connect the future global food demand to the role of agricultural and food science in producing and stabilising foods to meet the global food demand. We highlight the challenges to food and agriculture systems in the face of climate change and global megatrends that are shaping the future world. We discuss the opportunities to reduce food loss and waste, and recover produce that is currently wasted to make this the new raw ingredient supply for the food industry. Our systems-based perspective links food security to agricultural productivity, food safety, health and nutrition, processing and supply chain efficiency in the face of global and industry megatrends. We call for a collaborative, transdisciplinary approach to the science of food security, with a focus on enabling technologies within a context of social, market and global trends to achieve food and nutritional security.
Structural and Biochemical Characterization of AaL, a Quorum Quenching Lactonase with Unusual Kinetic Properties
Authors: Bergonzi Celine , Schwab Michael , Naik Tanushree , Daudé David , Chabrière Eric , Elias Mikael
Published: July 2018

Quorum quenching lactonases are enzymes that are capable of disrupting bacterial signaling based on acyl homoserine lactones (AHL) via their enzymatic degradation. In particular, lactonases have therefore been demonstrated to inhibit bacterial behaviors that depend on these chemicals, such as the formation of biofilms or the expression of virulence factors. Here we characterized biochemically and structurally a novel representative from the metallo-β-lactamase superfamily, named AaL that was isolated from the thermoacidophilic bacterium Alicyclobacillus acidoterrestris. AaL is a potent quorum quenching enzyme as demonstrated by its ability to inhibit the biofilm formation of Acinetobacter baumannii. Kinetic studies demonstrate that AaL is both a proficient and a broad spectrum enzyme, being capable of hydrolyzing a wide range of lactones with high rates (kcat/KM > 105 M−1.s−1). Additionally, AaL exhibits unusually low KM values, ranging from 10 to 80 µM. Analysis of AaL structures bound to phosphate, glycerol, and C6-AHL reveals a unique hydrophobic patch (W26, F87 and I237), involved in substrate binding, possibly accounting for the enzyme’s high specificity. Identifying the specificity determinants will aid the development of highly specific quorum quenching enzymes as potential therapeutics.
SVM-SulfoSite: A support vector machine based predictor for sulfenylation sites
Authors: AL-barakati Hussam J. , McConnell Evan W. , Hicks Leslie M. , Poole Leslie B. , Newman Robert H. , KC Dukka B.
Published: July 2018

ProteinS-sulfenylation, which results from oxidation of free thiols on cysteine residues, has recently emerged as an important post-translational modification that regulates the structure and function of proteins involved in a variety of physiological and pathological processes. By altering the size and physiochemical properties of modified cysteine residues, sulfenylation can impact the cellular function of proteins in several different ways. Thus, the ability to rapidly and accurately identify putative sulfenylation sites in proteins will provide important insights into redox-dependent regulation of protein function in a variety of cellular contexts. Though bottom-up proteomic approaches, such as tandem mass spectrometry (MS/MS), provide a wealth of information about global changes in the sulfenylation state of proteins, MS/MS-based experiments are often labor-intensive, costly and technically challenging. Therefore, to complement existing proteomic approaches, researchers have developed a series of computational tools to identify putative sulfenylation sites on proteins. However, existing methods often suffer from low accuracy, specificity, and/or sensitivity. In this study, we developed SVM-SulfoSite, a novel sulfenylation prediction tool that uses support vector machines (SVM) to identify key determinants of sulfenylation among five feature classes: binary code, physiochemical properties, k-space amino acid pairs, amino acid composition and high-quality physiochemical indices. Using 10-fold cross-validation, SVM-SulfoSite achieved 95% sensitivity and 83% specificity, with an overall accuracy of 89% and Matthew’s correlation coefficient (MCC) of 0.79. Likewise, using an independent test set of experimentally identified sulfenylation sites, our method achieved scores of 74%, 62%, 80% and 0.42 for accuracy, sensitivity, specificity and MCC, with an area under the receiver operator characteristic (ROC) curve of 0.81. Moreover, in side-by-side comparisons, SVM-SulfoSite performed as well as or better than existing sulfenylation prediction tools. Together, these results suggest that our method represents a robust and complementary technique for advanced exploration of protein S-sulfenylation.
Flavonoids inhibit cell proliferation and induce apoptosis and autophagy through downregulation of PI3Kγ mediated PI3K/AKT/mTOR/p70S6K/ULK signaling pathway in human breast cancer cells
Authors: Zhang Hong-Wei , Hu Jin-Jiao , Fu Ruo-Qiu , Liu Xin , Zhang Yan-Hao , Li Jing , Liu Lei , Li Yu-Nong , Deng Qin , Luo Qing-Song , Ouyang Qin , Gao Ning
Published: July 2018

Anticancer activities of flavonoids derived from Tephroseris kirilowii (Turcz.) Holub. were evaluated in human cancer cells. We isolated and identified, for the first time, eight flavonoids from T. kirilowii and found that three of them (IH: isorhamnetin, GN: genkwanin, and Aca: acacetin) inhibited cell proliferation in a variety of human cancer cell lines. These active flavonoids caused cell cycle arrest at G2/M phase and induced apoptosis and autophagy in human breast cancer cells. Molecular docking revealed that these flavonoids dock in the ATP binding pocket of PI3Kγ. Importantly, treatment with these flavonoids decreased the levels of PI3Kγ-p110, phospho-PI3K, phospho-AKT, phospho-mTOR, phospho-p70S6K, and phospho-ULK. Pretreatment with PI3Kγ specific inhibitor AS605240 potentiated flavonoids-mediated inactivation of AKT, mTOR, p70S6K, ULK, and apoptosis. Taken together, these findings represent a novel mechanism by which downregulation of PI3Kγ-p110 and consequent interruption of PI3K/AKT/mTOR/p70S6K/ULK signaling pathway might play a critical functional role in these flavonoids-induced cell cycle arrest at G2/M phase, apoptosis, and autophagy. Our studies provide novel insights into the anticancer activities of selected flavonoids and their potential uses in anticancer therapy.
Defining the frequency of human papillomavirus and polyomavirus infection in urothelial bladder tumours
Authors: Llewellyn Matthew A. , Gordon Naheema S. , Abbotts Ben , James Nicholas D. , Zeegers Maurice P. , Cheng K. K. , Macdonald Andrew , Roberts Sally , Parish Joanna L. , Ward Douglas G. , Bryan Richard T.
Published: July 2018

Given the contradictory nature of the literature regarding the role of human papillomaviruses and polyomaviruses in the pathogenesis of urothelial bladder cancer (UBC), we sought to investigate the frequency of their involvement in a large cohort of primary UBCs. DNA was extracted from 689 fresh-frozen UBC tissues and screened for the presence of high-risk human papillomavirus (HPV) types 16 and 18 and BKV/JCV genomic DNA by qPCR. In positive cases, viral identity was confirmed by Sanger sequencing and viral gene expression was analysed by RT-PCR or immunohistochemistry. All 689 UBCs were negative for HPV18. One UBC from a female patient with areas of squamous differentiation was positive for HPV16. The qPCR data indicated variable levels of polyomavirus in 49 UBCs. In the UBCs with low Cts we were able to confirm that 23 were BKV and 6 were JCV by Sanger sequencing. Polyomavirus large T antigen expression was low but detectable in 70% of the sequencing-confirmed polyomavirus positive samples. Thus, in United Kingdom patients, the presence of HPV DNA sequences is extremely rare in UBC (<1% of cases). Polyomavirus DNA (predominantly BKV) is more common in UBC, but still only detectable in 7% of cases and in many of these cases at low copy number. We have performed the largest virus screening to date in UBC, finding that HPV16, HPV18 and HPyV are unlikely to be common causative agents in UBC.
Zn2+-triggered self-assembly of Gonadorelin [6-D-Phe] to produce nanostructures and fibrils
Authors: Yordanova Yordanka , Vanderlinden Willem , Stoll Raphael , Rüdiger Daniel , Tosstorff Andreas , Zaremba Wolfgang , Winter Gerhard , Zahler Stefan , Friess Wolfgang
Published: July 2018

A synthetic derivative, GnRH [6-D-Phe], stable against enzymatic degradation, self-assembles and forms nanostructures and fibrils upon a pH shift in the presence of different concentrations of Zn2+in vitro. Attenuated Total Reflection Fourier Transform Infrared spectroscopy (ATR–FTIR) revealed the existence of higher order assembly of Zn2+: GnRH [6-D-Phe]. Nuclear Magnetic Resonance spectroscopy (NMR) indicated a weak interaction between Zn2+ and GnRH [6-D-Phe]. Atomic Force Microscopy (AFM) showed the existence of GnRH [6-D-Phe] oligomers and fibrils. Molecular Dynamic (MD) simulation of the 10:1 Zn2+: GnRH [6-D-Phe] explored the interaction and dimerization processes. In contrast to already existing short peptide fibrils, GnRH [6-D-Phe] nanostructures and fibrils form in a Tris-buffered pH environment in a controlled manner through a temperature reduction and a pH shift. The lyophilized Zn2+: GnRH [6-D-Phe] assembly was tested as a platform for the sustained delivery of GnRH [6-D-Phe] and incorporated into two different oil vehicle matrices. The in vitro release was slow and continuous over 14 days and not influenced by the oil matrix.
Questioning Seasonality of Neuronal Plasticity in the Adult Avian Brain
Authors: Pozner Tatyana , Vistoropsky Yulia , Moaraf Stan , Heiblum Rachel , Barnea Anat
Published: July 2018

To date, studies that reported seasonal patterns of adult neurogenesis and neuronal recruitment have correlated them to seasonal behaviors as the cause or as a consequence of neuronal changes. The aim of our study was to test this correlation, and to investigate whether there is a seasonal pattern of new neuronal recruitment that is not correlated to behavior. To do this, we used adult female zebra finches (songbirds that are not seasonal breeders), kept them under constant social, behavioral, and spatial environments, and compared neuronal recruitment in their brains during two seasons, under natural and laboratory conditions. Under natural conditions, no significant differences were found in the pattern of new neuronal recruitment across seasons. However, under artificial indoor conditions that imitated the natural conditions, higher neuronal recruitment occurred in late summer (August) compared to early spring (February). Moreover, our data indicate that “mixing” temperature and day length significantly reduces new neuronal recruitment, demonstrating the importance of the natural combination of temperature and day length. Taken together, our findings show, for the first time, that neuroplasticity changes under natural vs. artificial conditions, and demonstrate the importance of both laboratory and field experiments when looking at complex biological systems.
Galvanomagnetic properties of the putative type-II Dirac semimetal PtTe2
Authors: Pavlosiuk Orest , Kaczorowski Dariusz
Published: July 2018

Platinum ditelluride has recently been characterized, based on angle-resolved photoemission spectroscopy data and electronic band structure calculations, as a possible representative of type-II Dirac semimetals. Here, we report on the magnetotransport behavior (electrical resistivity, Hall effect) in this compound, investigated on high-quality single-crystalline specimens. The magnetoresistance (MR) of PtTe2 is large (over 3000% at T = 1.8 K in B = 9 T) and unsaturated in strong fields in the entire temperature range studied. The MR isotherms obey a Kohler’s type scaling with the exponent m = 1.69, different from the case of ideal electron-hole compensation. In applied magnetic fields, the resistivity shows a low-temperature plateau, characteristic of topological semimetals. In strong fields, well-resolved Shubnikov – de Haas (SdH) oscillations with two principle frequencies were found, and their analysis yielded charge mobilities of the order of 103 cm2 V−1 s−1 and rather small effective masses of charge carriers, 0.11 me and 0.21 me. However, the extracted Berry phases point to trivial character of the electronic bands involved in the SdH oscillations. The Hall effect data corroborated a multi-band character of the electrical conductivity in PtTe2, with moderate charge compensation.
Tear eicosanoids in healthy people and ocular surface disease
Authors: Ambaw Yohannes Abere , Chao Cecilia , Ji Shanshan , Raida Manfred , Torta Federico , Wenk Markus R. , Tong Louis
Published: July 2018

Meibomian gland (MG) dysfunction is the leading cause of evaporative dry eye and it leads to inflammation of the ocular surface. Eicosanoids may be involved in inflammation of dry eye. This study aimed to profile tear eicosanoid levels in healthy individuals and those with MG dysfunction, and to examine if these levels are associated with clinical factors and expressibility of MG. Forty participants with MG dysfunction and 30 healthy controls were recruited in this study. Clinical signs of MG dysfunction were assessed, and tear lactoferrin concentration was evaluated. Tear eicosanoids were extracted from Schirmer’s strips and analyzed using mass spectrometry. We were able to quantify 38 tear eicosanoids and levels were increased in older individuals. In participants with MG dysfunction, higher 5-HETE, LTB4, 18-HEPE, 12-HEPE and 14-HDoHE were associated with poorer MG expressibility. The eicosanoids PGF2α, 18-HEPE, 20-HDoHE and 17-HDoHE were elevated with increased corneal staining; higher 5-HETE, LTB4 were associated with lower tear lactoferrin levels. The receiver-operating-characteristics analysis shows higher levels of 5-HETE, LTB4 and 18-HEPE were able to predict poor expressibility of MGs. In conclusion, tear eicosanoid levels are age-dependent and specific eicosanoids may be indicators of clinical obstruction of MG or the severity of ocular surface damage.
Response of phytoplankton to heavy cloud cover and turbidity in the northern Bay of Bengal
Authors: Jyothibabu R. , Arunpandi N. , Jagadeesan L. , Karnan C. , Lallu K. R. , Vinayachandran P. N.
Published: July 2018

An interesting physiological response of phytoplankton to large fluctuations in underwater photosynthetically active radiation (PAR) levels in the northern Bay of Bengal has been presented here. This study is primarily based on a 12-day time series observation in the northern Bay of Bengal during the peak Southwest Monsoon (July 2012), when the study region was recurrently exposed to alternating cloudy and sunny sky conditions. On overcast days, the PAR available underwater at the time series location (TSL) drastically decreased, with the noontime PAR at the surface water (2 m) usually being ~600 µmol m−2 s−1 on sunny days and declining to ~50 µmol m−2 s−1 on heavily overcast days. Closely linked with the sunny and cloudy days at TSL, chlorophyll a concentration in the water column showed noticeable features; it increased in the upper water column (surface-40 m) and decreased in the lower water column (41–80 m) on cloudy days, while the reverse was the case on sunny days. Based on in-situ and laboratory experimental data, it was observed that these temporal changes in the vertical distribution of chlorophyll a in the northern Bay of Bengal were due to the short-term physiological acclimation of phytoplankton to large changes in underwater PAR.
Small litter size impairs spatial memory and increases anxiety- like behavior in a strain-dependent manner in male mice
Authors: Salari Ali-Akbar , Samadi Hanieh , Homberg Judith R. , Kosari-Nasab Morteza
Published: July 2018

Early life overfeeding is associated with cognitive decline and anxiety-like behaviors in later life. It is not clear whether there are individual differences in the effects of early life overfeeding and what the underlying mechanistic pathways are. We investigated the long-lasting effects of small litter size, an experimental manipulation to induce neonatal overfeeding, in two strains of mice, C57BL/6 and NMRI. We measured body weight, learning and memory, anxiety-related behaviors, interleukin-(IL)-1β and brain-derived-neurotrophic-factor (BDNF) levels in the hippocampus, and both basal and stress corticosterone levels in adult mice which have been nursed in small litters compared with those from control litters. Our findings showed that small litter size led to increased body weight in both strains of mice. Small litter size significantly decreased spatial memory and hippocampal BDNF levels, and increased hippocampal IL-1β, in NMRI mice, but not C57BL/6 mice. Interestingly, we found that small litter size resulted in a significant increase in anxiety-like behaviors and stress-induced corticosterone in NMRI mice, whereas small litter size reduced anxiety-like symptoms and stress-induced corticosterone levels in C57BL/6 mice. These data show that small litter size, which is life-long associated with increased body weight, affects memory and anxiety-related behaviors in a strain-dependent manner in male mice. This suggests that there are individual differences in the developmental consequences of early life overfeeding.
Quantitative Profiling of the Lymph Node Clearance Capacity
Authors: Clement Cristina C. , Wang Wei , Dzieciatkowska Monika , Cortese Marco , Hansen Kirk C. , Becerra Aniuska , Thangaswamy Sangeetha , Nizamutdinova Irina , Moon Jee-Young , Stern Lawrence J. , Gashev Anatoliy A. , Zawieja David , Santambrogio Laura
Published: July 2018

Transport of tissue-derived lymphatic fluid and clearance by draining lymph nodes are pivotal for maintenance of fluid homeostasis in the body and for immune-surveillance of the self- and non-self-proteomes. Yet a quantitative analysis of nodal filtration of the tissue-derived proteome present in lymphatic fluid has not been reported. Here we quantified the efficiency of nodal clearance of the composite proteomic load using label-free and isotope-labeling proteomic analysis of pre-nodal and post-nodal samples collected by direct cannulation. These results were extended by quantitation of the filtration efficiency of fluorophore-labeled proteins, bacteria, and beads infused at physiological flow rates into pre-nodal lymphatic collectors and collected by post-nodal cannulation. We developed a linear model of nodal filtration efficiency dependent on pre-nodal protein concentrations and molecular weight, and uncovered criteria for disposing the proteome incoming from defined anatomical districts under physiological conditions. These findings are pivotal to understanding the maximal antigenic load sustainable by a draining node, and promote understanding of pathogen spreading and nodal filtration of tumor metastasis, potentially helping to improve design of vaccination protocols, immunization strategies and drug delivery.
Crystal structure of the membrane attack complex assembly inhibitor BGA71 from the Lyme disease agent Borrelia bavariensis
Authors: Brangulis Kalvis , Akopjana Inara , Petrovskis Ivars , Kazaks Andris , Kraiczy Peter , Tars Kaspars
Published: July 2018

Borrelia (B.) bavariensis, B. burgdorferi, B. afzelii, B. garinii, B. spielmanii, and B. mayonii are the causative agents in Lyme disease. Lyme disease spirochetes reside in infected Ixodes ticks and are transferred to mammalian hosts during tick feeding. Once transmitted, spirochetes must overcome the first line of defense of the innate immune system either by binding complement regulators or by terminating the formation of the membrane attack complex (MAC). In B. bavariensis, the proteins BGA66 and BGA71 inhibit complement activation by interacting with the late complement components C7, C8, and C9, as well as with the formed MAC. In this study, we have determined the crystal structure of the potent MAC inhibitor BGA71 at 2.9 Ǻ resolution. The structure revealed a cysteine cross-linked homodimer. Based on the crystal structure of BGA71 and the structure-based sequence alignment with CspA from B. burgdorferi, we have proposed a potential binding site for C7 and C9, both of which are constituents of the formed MAC. Our results shed light on the molecular mechanism of immune evasion developed by the human pathogenic Borrelia species to overcome innate immunity. These results will aid in the understanding of Lyme disease pathogenesis and pave the way for the development of new strategies to prevent Lyme disease.
Assessment of High Thermal Effects on Carbon Nanotube (Cnt)- Reinforced Concrete
Authors: Elkady Hala , Hassan Ahmed
Published: July 2018

This paper presents the outcome of a project funded by Beni-suef University targeting the assessment of the addition of carbon nanotubes (CNTs) to reinforced concrete beams on exposure to elevated temperatures. Tests were carried out in compliance to ASTM E119-95a. Besides, pre and post their exposure to elevated temperature tests, the maximum bending capacity of the beams are evaluated. Standard reinforced concrete beams are cast- with and without Carbon Nanotube (CNT). Tests were performed at two temperature levels 400 °C and 600 °C working around temperature ranges expected to have significant effect on concrete endurance, using both one and two hours exposure. Results proved a positive effect for adding CNT to beams at room temperature. This improvement is slightly affected at 400 °C exposure for 2 hr. On the other hand, exposing CNT beams for 600 °C for two hours reduced the beams capacity by 14% compared to a similar reinforced beam without CNT. It is worth notice that CNT was not burnt but suffered de-bonding. Finally, this investigation implies that CNT can be used as an enhancing element to concrete ductility, with no deterioration in other mechanical characteristics on exposure to drastic thermal conditions.