bluuebunny/crossref_metadata_2025 huggingface dataset:
Cover Crop and Postemergence Herbicide Integration for Palmer amaranth Control in Cotton
Authors: Wiggins Matthew S. , Hayes Robert M. , Nichols Robert L. , Steckel Lawrence E.
Published: May 2017

Field experiments were conducted to evaluate the integration of cover crops and POST herbicides to control glyphosate-resistant Palmer amaranth in cotton. The winter-annual grasses accumulated the greatest amount of biomass and provided the most Palmer amaranth control. The estimates for the logistic regression would indicate that 1540 kg ha−1would delay Palmer amaranth emerging and growing to 10 cm by an estimated 16.5 days. The Palmer amaranth that emerged in the cereal rye and wheat cover crop treatments took a longer time to reach 10 cm compared to the hairy vetch and crimson clover treatments. POST herbicides were needed for adequate control of Palmer amaranth. The glufosinate-based weed control system provided greater control (75% vs 31%) of Palmer amaranth than did the glyphosate system. These results indicate that a POST only herbicide weed management system did not provide sufficient control of Palmer amaranth, even when used in conjunction with cover crops that produced a moderate level of biomass. Therefore, future recommendations for GR Palmer amaranth control will include integrating cover crops with PRE herbicides, overlaying residual herbicides in-season, timely POST herbicide applications, and hand weeding in order to achieve season-long control of this pest.
With 2017 Budget Signed into Law, Eyes Turn to 2018 Battle
Authors: Showstack Randy
Published: May 2017

Analysts hope that Congress will continue to support science programs in next year’s budget as well.
Large polarization gradients and temperature-stable responses in compositionally-graded ferroelectrics
Authors: Damodaran Anoop R. , Pandya Shishir , Qi Yubo , Hsu Shang-Lin , Liu Shi , Nelson Christopher , Dasgupta Arvind , Ercius Peter , Ophus Colin , Dedon Liv R. , Agar Josh C. , Lu Hongling , Zhang Jialan , Minor Andrew M. , Rappe Andrew M. , Martin Lane W.
Published: May 2017

A range of modern applications require large and tunable dielectric, piezoelectric or pyroelectric response of ferroelectrics. Such effects are intimately connected to the nature of polarization and how it responds to externally applied stimuli. Ferroelectric susceptibilities are, in general, strongly temperature dependent, diminishing rapidly as one transitions away from the ferroelectric phase transition (TC). In turn, researchers seek new routes to manipulate polarization to simultaneously enhance susceptibilities and broaden operational temperature ranges. Here, we demonstrate such a capability by creating composition and strain gradients in Ba1−xSrxTiO3 films which result in spatial polarization gradients as large as 35 μC cm−2 across a 150 nm thick film. These polarization gradients allow for large dielectric permittivity with low loss (ɛr≈775, tan δ<0.05), negligible temperature-dependence (13% deviation over 500 °C) and high-dielectric tunability (greater than 70% across a 300 °C range). The role of space charges in stabilizing polarization gradients is also discussed.
Antibody targeting intracellular oncogenic Ras mutants exerts anti-tumour effects after systemic administration
Authors: Shin Seung-Min , Choi Dong-Ki , Jung Keunok , Bae Jeomil , Kim Ji-sun , Park Seong-wook , Song Ki-Hoon , Kim Yong-Sung
Published: May 2017

Oncogenic Ras mutants, frequently detected in human cancers, are high-priority anticancer drug targets. However, direct inhibition of oncogenic Ras mutants with small molecules has been extremely challenging. Here we report the development of a human IgG1 format antibody, RT11, which internalizes into the cytosol of living cells and selectively binds to the activated GTP-bound form of various oncogenic Ras mutants to block the interactions with effector proteins, thereby suppressing downstream signalling and exerting anti-proliferative effects in a variety of tumour cells harbouring oncogenic Ras mutants. When systemically administered, an RT11 variant with an additional tumour-associated integrin binding moiety for tumour tissue targeting significantly inhibits the in vivo growth of oncogenic Ras-mutated tumour xenografts in mice, but not wild-type Ras-harbouring tumours. Our results demonstrate the feasibility of developing therapeutic antibodies for direct targeting of cytosolic proteins that are inaccessible using current antibody technology.
Actively addressed single pixel full-colour plasmonic display
Authors: Franklin Daniel , Frank Russell , Wu Shin-Tson , Chanda Debashis
Published: May 2017

Dynamic, colour-changing surfaces have many applications including displays, wearables and active camouflage. Plasmonic nanostructures can fill this role by having the advantages of ultra-small pixels, high reflectivity and post-fabrication tuning through control of the surrounding media. However, previous reports of post-fabrication tuning have yet to cover a full red-green-blue (RGB) colour basis set with a single nanostructure of singular dimensions. Here, we report a method which greatly advances this tuning and demonstrates a liquid crystal-plasmonic system that covers the full RGB colour basis set, only as a function of voltage. This is accomplished through a surface morphology-induced, polarization-dependent plasmonic resonance and a combination of bulk and surface liquid crystal effects that manifest at different voltages. We further demonstrate the system’s compatibility with existing LCD technology by integrating it with a commercially available thin-film-transistor array. The imprinted surface interfaces readily with computers to display images as well as video.
Light-induced unfolding and refolding of supramolecular polymer nanofibres
Authors: Adhikari Bimalendu , Yamada Yuki , Yamauchi Mitsuaki , Wakita Kengo , Lin Xu , Aratsu Keisuke , Ohba Tomonori , Karatsu Takashi , Hollamby Martin J. , Shimizu Nobutaka , Takagi Hideaki , Haruki Rie , Adachi Shin-ichi , Yagai Shiki
Published: May 2017

Unlike classical covalent polymers, one-dimensionally (1D) elongated supramolecular polymers (SPs) can be encoded with high degrees of internal order by the cooperative aggregation of molecular subunits, which endows these SPs with extraordinary properties and functions. However, this internal order has not yet been exploited to generate and dynamically control well-defined higher-order (secondary) conformations of the SP backbone, which may induce functionality that is comparable to protein folding/unfolding. Herein, we report light-induced conformational changes of SPs based on the 1D exotic stacking of hydrogen-bonded azobenzene hexamers. The stacking causes a unique internal order that leads to spontaneous curvature, which allows accessing conformations that range from randomly folded to helically folded coils. The reversible photoisomerization of the azobenzene moiety destroys or recovers the curvature of the main chain, which demonstrates external control over the SP conformation that may ultimately lead to biological functions.
TRPV1 channels are critical brain inflammation detectors and neuropathic pain biomarkers in mice
Authors: Marrone Maria Cristina , Morabito Annunziato , Giustizieri Michela , Chiurchiù Valerio , Leuti Alessandro , Mattioli Marzia , Marinelli Sara , Riganti Loredana , Lombardi Marta , Murana Emanuele , Totaro Antonio , Piomelli Daniele , Ragozzino Davide , Oddi Sergio , Maccarrone Mauro , Verderio Claudia , Marinelli Silvia
Published: May 2017

The capsaicin receptor TRPV1 has been widely characterized in the sensory system as a key component of pain and inflammation. A large amount of evidence shows that TRPV1 is also functional in the brain although its role is still debated. Here we report that TRPV1 is highly expressed in microglial cells rather than neurons of the anterior cingulate cortex and other brain areas. We found that stimulation of microglial TRPV1 controls cortical microglia activation per se and indirectly enhances glutamatergic transmission in neurons by promoting extracellular microglial microvesicles shedding. Conversely, in the cortex of mice suffering from neuropathic pain, TRPV1 is also present in neurons affecting their intrinsic electrical properties and synaptic strength. Altogether, these findings identify brain TRPV1 as potential detector of harmful stimuli and a key player of microglia to neuron communication.
Heterodimerization of Munc13 C2A domain with RIM regulates synaptic vesicle docking and priming
Authors: Camacho Marcial , Basu Jayeeta , Trimbuch Thorsten , Chang Shuwen , Pulido-Lozano Cristina , Chang Shwu-Shin , Duluvova Irina , Abo-Rady Masin , Rizo Josep , Rosenmund Christian
Published: May 2017

The presynaptic active zone protein Munc13 is essential for neurotransmitter release, playing key roles in vesicle docking and priming. Mechanistically, it is thought that the C2A domain of Munc13 inhibits the priming function by homodimerization, and that RIM disrupts the autoinhibitory homodimerization forming monomeric priming-competent Munc13. However, it is unclear whether the C2A domain mediates other Munc13 functions in addition to this inactivation–activation switch. Here, we utilize mutations that modulate the homodimerization and heterodimerization states to define additional roles of the Munc13 C2A domain. Using electron microscopy and electrophysiology in hippocampal cultures, we show that the C2A domain is critical for additional steps of vesicular release, including vesicle docking. Optimal vesicle docking and priming is only possible when Munc13 heterodimerizes with RIM via its C2A domain. Beyond being a switching module, our data suggest that the Munc13-RIM heterodimer is an active component of the vesicle docking, priming and release complex.
Hybrid supercapacitors for reversible control of magnetism
Authors: Molinari Alan , Leufke Philipp M. , Reitz Christian , Dasgupta Subho , Witte Ralf , Kruk Robert , Hahn Horst
Published: May 2017

Electric field tuning of magnetism is one of the most intensely pursued research topics of recent times aiming at the development of new-generation low-power spintronics and microelectronics. However, a reversible magnetoelectric effect with an on/off ratio suitable for easy and precise device operation is yet to be achieved. Here we propose a novel route to robustly tune magnetism via the charging/discharging processes of hybrid supercapacitors, which involve electrostatic (electric-double-layer capacitance) and electrochemical (pseudocapacitance) doping. We use both charging mechanisms—occurring at the La0.74Sr0.26MnO3/ionic liquid interface to control the balance between ferromagnetic and non-ferromagnetic phases of La1−xSrxMnO3 to an unprecedented extent. A magnetic modulation of up to ≈33% is reached above room temperature when applying an external potential of only about 2.0 V. Our case study intends to draw attention to new, reversible physico-chemical phenomena in the rather unexplored area of magnetoelectric supercapacitors.
Learning stable and predictive network-based patterns of schizophrenia and its clinical symptoms
Authors: Gheiratmand Mina , Rish Irina , Cecchi Guillermo A. , Brown Matthew R. G. , Greiner Russell , Polosecki Pablo I. , Bashivan Pouya , Greenshaw Andrew J. , Ramasubbu Rajamannar , Dursun Serdar M.
Published: May 2017

Schizophrenia is often associated with disrupted brain connectivity. However, identifying specific neuroimaging-based patterns pathognomonic for schizophrenia and related symptom severity remains a challenging open problem requiring large-scale data-driven analyses emphasizing not only statistical significance but also stability across multiple datasets, contexts and cohorts. Accurate prediction on previously unseen subjects, or generalization, is also essential for any useful biomarker of schizophrenia. In order to build a predictive model based on functional network feature patterns, we studied whole-brain fMRI functional networks, both at the voxel level and lower-resolution supervoxel level. Targeting Auditory Oddball task data on the FBIRN fMRI dataset (n = 95), we considered node-degree and link-weight network features and evaluated stability and generalization accuracy of statistically significant feature sets in discriminating patients vs. controls. We also applied sparse multivariate regression (elastic net) to whole-brain functional connectivity features, for the first time, to derive stable predictive features for symptom severity. Whole-brain link-weight features achieved 74% accuracy in identifying patients and were more stable than voxel-wise node-degrees. Link-weight features predicted severity of several negative and positive symptom scales, including inattentiveness and bizarre behavior. The most-significant, stable and discriminative functional connectivity changes involved increased correlations between thalamus and primary motor/primary sensory cortex, and between precuneus (BA7) and thalamus, putamen, and Brodmann areas BA9 and BA44. Precuneus, along with BA6 and primary sensory cortex, was also involved in predicting severity of several symptoms. Overall, the proposed multi-step methodology may help identify more reliable multivariate patterns allowing for accurate prediction of schizophrenia and its symptoms severity.
Development of a Whole Organism Platform for Phenotype-Based Analysis of IGF1R-PI3K-Akt-Tor Action
Authors: Liu Chengdong , Dai Wei , Bai Yan , Chi Changfeng , Xin Yi , He Gen , Mai Kangsen , Duan Cunming
Published: May 2017

Aberrant regulation of the insulin-like growth factor (IGF)/insulin (IIS)-PI3K-AKT-TOR signaling pathway is linked to major human diseases, and key components of this pathway are targets for therapeutic intervention. Current assays are molecular target- or cell culture-based platforms. Due to the great in vivo complexities inherited in this pathway, there is an unmet need for whole organism based assays. Here we report the development of a zebrafish transgenic line, Tg(igfbp5a:GFP), which faithfully reports the mitotic action of IGF1R-PI3K-Akt-Tor signaling in epithelial cells in real-time. This platform is well suited for high-throughput assays and real-time cell cycle analysis. Using this platform, the dynamics of epithelial cell proliferation in response to low [Ca2+] stress and the distinct roles of Torc1 and Torc2 were elucidated. The availability of Tg(igfbp5a:GFP) line provides a whole organism platform for phenotype-based discovery of novel players and inhibitors in the IIS-PI3K-Akt-Tor signaling pathway.
Using an Event-History with Risk-Free Model to Study the Genetics of Alcoholism
Authors: Yang Hsin-Chou , Chen I-Chen , Tsay Yuh-Chyuan , Li Zheng-Rong , Chen Chun-houh , Hwu Hai-Gwo , Chen Chen-Hsin
Published: May 2017

Case–control genetic association studies typically ignore possible later disease onset in currently healthy subjects and assume that subjects with diseases equally contribute to the likelihood for inference, regardless of their onset age. Therefore, we used an event-history with risk-free model to simultaneously characterize alcoholism susceptibility and onset age in 65 independent non-Hispanic Caucasian males in the Collaborative Study on the Genetics of Alcoholism. Following data quality control, we analysed 22 single nucleotide polymorphisms (SNPs) on 12 candidate genes. The single-SNP analysis showed that the dominant minor allele of rs2134655 onDRD3increases alcoholism susceptibility; the dominant minor allele of rs1439047 onNTRK2delays the alcoholism onset age, but the additive minor allele of rs172677 onGRIN2Band the dominant minor allele of rs63319 onALDH1A1advance the alcoholism onset age; and the dominant minor allele of rs1079597 onDRD2shortens the onset age range. Similarly, multiple-SNPs analysis revealed joint effects of rs2134655, rs172677 and rs1079597, with an adjustment for habitual smoking. This study provides a more comprehensive understanding of the genetics of alcoholism than previous case–control studies.
Microfluidic Sorting of Cells by Viability Based on Differences in Cell Stiffness
Authors: Islam Muhymin , Brink Hannah , Blanche Syndey , DiPrete Caleb , Bongiorno Tom , Stone Nicholas , Liu Anna , Philip Anisha , Wang Gonghao , Lam Wilbur , Alexeev Alexander , Waller Edmund K. , Sulchek Todd
Published: May 2017

The enrichment of viable cells is an essential step to obtain effective products for cell therapy. While procedures exist to characterize the viability of cells, most methods to exclude nonviable cells require the use of density gradient centrifugation or antibody-based cell sorting with molecular labels of cell viability. We report a label-free microfluidic technique to separate live and dead cells that exploits differences in cellular stiffness. The device uses a channel with repeated ridges that are diagonal with respect to the direction of cell flow. Stiff nonviable cells directed through the channel are compressed and translated orthogonally to the channel length, while soft live cells follow hydrodynamic flow. As a proof of concept, Jurkat cells are enriched to high purity of viable cells by a factor of 185-fold. Cell stiffness was validated as a sorting parameter as nonviable cells were substantially stiffer than live cells. To highlight the utility for hematopoietic stem cell transplantation, frozen samples of cord blood were thawed and the purity of viable nucleated cells was increased from 65% to over 94% with a recovery of 73% of the viable cells. Thus, the microfluidic stiffness sorting can simply and efficiently obtain highly pure populations of viable cells.
The Topobiology of Chemical Elements in Seabird Feathers
Authors: R. Howell Nicholas , Lavers Jennifer L. , Uematsu Sayaka , Paterson David , Howard Daryl L. , Spiers Kathryn , Jonge Martin D. de , Hanley Tracey , Garrett Richard , Banati Richard B.
Published: May 2017

The highly organized morphogenesis of bird feathers holds important phylo- and ontogenetic information on the evolution of birds, organogenesis, tissue regeneration, and the health status of individual animals. Altered topobiological patterns are regularly used as retrospective evidence for disturbed developmental trajectories due to the past exposure to environmental stressors. Using the most advanced high-resolution (5–70 µm) X-ray fluorescence microscopy (XFM), we describe in the feathers from three species of Procellariiformes hitherto unknown, depositions of elements (Zn, Ca, Br, Cu, Fe) that are independent of pigmentation or any underlying variation in density or polymer structure. In the case of Zn, the pattern across several species of Procellariiformes, but not other species, consisted of highly regular bands of Zn numbering 30–32, which may reflect the estimated number of days of active feather growth or the duration of the moult period. Thus, speculatively, the highly consistent Zn pattern might be the result of a so far unknown diurnal systemic regulation rather than local heterogeneity amongst the follicular stem cells.
Vascular Remodelling Relates to an Elevated Oscillatory Shear Index and Relative Residence Time in Spontaneously Hypertensive Rats
Authors: Chen Zhiyan , Yu Haiyi , Shi Yue , Zhu Minjia , Wang Yueshen , Hu Xi , Zhang Youyi , Chang Yu , Xu Ming , Gao Wei
Published: May 2017

Haemodynamic disorders are common clinical findings in hypertension and lead to adverse cardiovascular events. However, the haemodynamic conditions in hypertension models are poorly understood. This study aimed to observe the characteristics of haemodynamics in spontaneously hypertensive rats (SHRs) and antihypertensive-treated SHRs. Twenty-four adult male SHRs and Wistar-Kyoto rats (WKYs) were randomly divided into four groups and treated for 7 days as follows: WKY-CON (WKYs + saline), WKY-NIF (WKYs + nifedipine, 50 mg/kg/day), SHR-CON (SHRs + saline), and SHR-NIF (SHRs + nifedipine). Aortic computational fluid dynamics (CFD) models were simulated to obtain the haemodynamic parameters. We found that in the hypertensive (SHR-CON) and blood pressure-controlled (SHR-NIF) groups, the oscillatory shear index (OSI) and relative residence time (RRT), which are key haemodynamics indices, were markedly elevated. Furthermore, there was a correlation between both the elevated OSI and RRT with the vascular wall thickening in regions near the inner wall of the aortic arch. Our research demonstrates that haemodynamics remains disturbed even if the blood pressure is normalized. In addition, vascular remodelling may play an important role in maintaining elevated OSI and RRT values.
The role of stride frequency for walk-to-run transition in humans
Authors: Hansen Ernst Albin , Kristensen Lasse Andreas Risgaard , Nielsen Andreas Møller , Voigt Michael , Madeleine Pascal
Published: May 2017

It remains unclear why humans spontaneously shift from walking to running at a certain point during locomotion at gradually increasing velocity. We show that a calculated walk-to-run transition stride frequency (70.6 ± 3.2 strides min−1) agrees with a transition stride frequency (70.8 ± 3.1 strides min−1) predicted from the two stride frequencies applied during treadmill walking and running at freely chosen velocities and freely chosen stride frequencies. The agreement is based on Bland and Altman’s statistics. We found no essential mean relative difference between the two transition frequencies, i.e. −0.5% ± 4.2%, as well as limits of agreement of −8.7% and 7.7%. The particular two freely chosen stride frequencies used for prediction are considered behavioural attractors. Gait is predicted to be shifted from walking to running when the stride frequency starts getting closer to the running attractor than to the walking attractor. In particular, previous research has focussed on transition velocity and optimisation theories based on minimisation of, e.g., energy turnover or biomechanical loadings of the legs. Conversely, our data support that the central phenomenon of walk-to-run transition during human locomotion could be influenced by behavioural attractors in the form of stride frequencies spontaneously occurring during behaviourally unrestricted gait conditions of walking and running.
Global gene expression analysis provides insight into local adaptation to geothermal streams in tadpoles of the Andean toad Rhinella spinulosa
Authors: Pastenes Luis , Valdivieso Camilo , Di Genova Alex , Travisany Dante , Hart Andrew , Montecino Martín , Orellana Ariel , Gonzalez Mauricio , Gutiérrez Rodrigo A. , Allende Miguel L. , Maass Alejandro , Méndez Marco A.
Published: May 2017

The anuran Rhinella spinulosa is distributed along the Andes Range at altitudes that undergo wide daily and seasonal variation in temperature. One of the populations inhabits geothermal streams, a stable environment that influences life history traits such as the timing of metamorphosis. To investigate whether this population has undergone local adaptation to this unique habitat, we carried out transcriptome analyses in animals from two localities in two developmental stages (prometamorphic and metamorphic) and exposed them to two temperatures (20 and 25 °C). RNA-Seq, de novo assembly and annotation defined a transcriptome revealing 194,469 high quality SNPs, with 1,507 genes under positive selection. Comparisons among the experimental conditions yielded 1,593 differentially expressed genes. A bioinformatics search for candidates revealed a total of 70 genes that are highly likely to be implicated in the adaptive response of the population living in a stable environment, compared to those living in an environment with variable temperatures. Most importantly, the population inhabiting the geothermal environment showed decreased transcriptional plasticity and reduced genetic variation compared to its counterpart from the non-stable environment. This analysis will help to advance the understanding of the molecular mechanisms that account for the local adaptation to geothermal streams in anurans.
Three-dimensional scoring of zebrafish behavior unveils biological phenomena hidden by two-dimensional analyses
Authors: Macrì Simone , Neri Daniele , Ruberto Tommaso , Mwaffo Violet , Butail Sachit , Porfiri Maurizio
Published: May 2017

The study of zebrafish behavior represents a cornerstone upon which basic researchers promise to advance knowledge in life sciences. Although zebrafish swim in a three-dimensional (3D) space, their behavior in the lab is almost exclusively scored in two dimensions, whereby zebrafish are recorded using a single camera providing 2D videos. Whether this dimensional reduction preserves the reliability of data has not been addressed. Here we show that, compared to a 3D observation, 2D data are flawed by over-reporting and under-reporting of locomotory differences. Specifically, we first reconstructed 3D trajectories through the integration of synchronous information derived from two cameras, and then compared them with the original 2D views in classical experimental paradigms assessing shoaling tendency, fear, anxiety, and general locomotion. Our results suggest that traditional behavioral scoring of individual zebrafish performed in 2D may undermine data integrity, thereby requiring a general reconsideration of scoring zebrafish behavior to incorporate a 3D approach. We then demonstrate that, compared to 2D, a 3D approach requires a reduced number of subjects to achieve the same degree of validity. We anticipate these findings to largely benefit animal welfare by reducing the number of experimental subjects, without affecting statistical power.
cAMP-dependent cell differentiation triggered by activated CRHR1 in hippocampal neuronal cells
Authors: Inda Carolina , Bonfiglio Juan José , dos Santos Claro Paula A. , Senin Sergio A. , Armando Natalia G. , Deussing Jan M. , Silberstein Susana
Published: May 2017

Corticotropin-releasing hormone receptor 1 (CRHR1) activates the atypical soluble adenylyl cyclase (sAC) in addition to transmembrane adenylyl cyclases (tmACs). Both cAMP sources were shown to be required for the phosphorylation of ERK1/2 triggered by activated G protein coupled receptor (GPCR) CRHR1 in neuronal and neuroendocrine contexts. Here, we show that activated CRHR1 promotes growth arrest and neurite elongation in neuronal hippocampal cells (HT22-CRHR1 cells). By characterising CRHR1 signalling mechanisms involved in the neuritogenic effect, we demonstrate that neurite outgrowth in HT22-CRHR1 cells takes place by a sAC-dependent, ERK1/2-independent signalling cascade. Both tmACs and sAC are involved in corticotropin-releasing hormone (CRH)-mediated CREB phosphorylation and c-fos induction, but only sAC-generated cAMP pools are critical for the neuritogenic effect of CRH, further highlighting the engagement of two sources of cAMP downstream of the activation of a GPCR, and reinforcing the notion that restricted cAMP microdomains may regulate independent cellular processes.
Entanglement monogamy in three qutrit systems
Authors: Li Qiting , Cui Jianlian , Wang Shuhao , Long Gui-Lu
Published: May 2017

By introducing an arbitrary-dimensional multipartite entanglement measure, which is defined in terms of the reduced density matrices corresponding to all possible two partitions of the entire system, we prove that multipartite entanglement cannot be freely shared among the parties in both n-qubit systems and three-qutrit systems. Furthermore, our result implies that the satisfaction of the entanglement monogamy is related to the number of particles in the quantum system. As an application of three-qutrit monogamy inequality, we give a condition for the separability of a class of two-qutrit mixed states in a 3 ⊗ 3 system.
FGF23/FGFR4-mediated left ventricular hypertrophy is reversible
Authors: Grabner Alexander , Schramm Karla , Silswal Neerupma , Hendrix Matt , Yanucil Christopher , Czaya Brian , Singh Saurav , Wolf Myles , Hermann Sven , Stypmann Jörg , Di Marco Giovana Seno , Brand Marcus , Wacker Michael J. , Faul Christian
Published: May 2017

Fibroblast growth factor (FGF) 23 is a phosphaturic hormone that directly targets cardiac myocytes via FGF receptor (FGFR) 4 thereby inducing hypertrophic myocyte growth and the development of left ventricular hypertrophy (LVH) in rodents. Serum FGF23 levels are highly elevated in patients with chronic kidney disease (CKD), and it is likely that FGF23 directly contributes to the high rates of LVH and cardiac death in CKD. It is currently unknown if the cardiac effects of FGF23 are solely pathological, or if they potentially can be reversed. Here, we report that FGF23-induced cardiac hypertrophy is reversible in vitro and in vivo upon removal of the hypertrophic stimulus. Specific blockade of FGFR4 attenuates established LVH in the 5/6 nephrectomy rat model of CKD. Since CKD mimics a form of accelerated cardiovascular aging, we also studied age-related cardiac remodeling. We show that aging mice lacking FGFR4 are protected from LVH. Finally, FGF23 increases cardiac contractility via FGFR4, while known effects of FGF23 on aortic relaxation do not require FGFR4. Taken together, our data highlight a role of FGF23/FGFR4 signaling in the regulation of cardiac remodeling and function, and indicate that pharmacological interference with cardiac FGF23/FGFR4 signaling might protect from CKD- and age-related LVH.
Two-step phase shifting differential-recording digital holographic microscopy
Authors: Han Jun-He , Li Ruo-Ping , Liu Jun-Hui , Hai Fu-Sheng , Huang Ming-Ju
Published: May 2017

We present two-step phase-shifting differential-recording digital holographic microscopy (TPD-DH in microscopy) for phase imaging of microscopic transparent elements. Two CCDs are employed to record two interferograms at two different defocusing distances. The interferograms on the two CCD cameras are shifted for a phase retarder 0 and π via an all-optics phase shifting unit. A novel algorithm is proposed to reconstruct both amplitude and phase distributions of the object wave from the recorded interferograms. This method has the same spectrum bandwidth and measurement accuracy with those of conventional four-step phase-shifting interferometry (FS-PSI), whereas it reduces the measurement time by half.
Characterization of Mechanically Matched Hydrogel Coatings to Improve the Biocompatibility of Neural Implants
Authors: Spencer Kevin C. , Sy Jay C. , Ramadi Khalil B. , Graybiel Ann M. , Langer Robert , Cima Michael J.
Published: May 2017

Glial scar is a significant barrier to neural implant function. Micromotion between the implant and tissue is suspected to be a key driver of glial scar formation around neural implants. This study explores the ability of soft hydrogel coatings to modulate glial scar formation by reducing local strain. PEG hydrogels with controllable thickness and elastic moduli were formed on the surface of neural probes. These coatings significantly reduced the local strain resulting from micromotion around the implants. Coated implants were found to significantly reduce scarring in vivo, compared to hard implants of identical diameter. Increasing implant diameter was found to significantly increase scarring for glass implants, as well as increase local BBB permeability, increase macrophage activation, and decrease the local neural density. These results highlight the tradeoff in mechanical benefit with the size effects from increasing the overall diameter following the addition of a hydrogel coating. This study emphasizes the importance of both mechanical and geometric factors of neural implants on chronic timescales.
DLX3 interacts with GCM1 and inhibits its transactivation-stimulating activity in a homeodomain-dependent manner in human trophoblast-derived cells
Authors: Li Sha , Roberson Mark S.
Published: May 2017

The placental transcription factors Distal-less 3 (DLX3) and Glial cell missing-1 (GCM1) have been shown to coordinate the specific regulation of PGF in human trophoblast cell lines. While both factors independently have a positive effect on PGF gene expression, when combined, DLX3 acts as an antagonist to GCM. Despite this understanding, potential mechanisms accounting for this regulatory interaction remain unexplored. We identify physical and functional interactions between specific domains of DLX3 and GCM1 in human trophoblast-derived cells by performing immunoprecipitation and mammalian one hybrid assays. Studies revealed that DLX3 binding reduced the transcriptional activity of GCM1, providing a mechanistic explanation of their functional antagonism in regulating PGF promoter activity. The DLX3 homeodomain (HD) was essential for DLX3-GCM1 interaction, and that the HD together with the DLX3 amino- or carboxyl-terminal domains was required for maximal inhibition of GCM1. Interestingly, a naturally occurring DLX3 mutant that disrupts the carboxyl-terminal domain leading to tricho-dento-osseous syndrome in humans displayed activities indistinguishable from wild type DLX3 in this system. Collectively, our studies demonstrate that DLX3 physically interacts with GCM1 and inhibits its transactivation activity, suggesting that DLX3 and GCM1 may form a complex to functionally regulate placental cell function through modulation of target gene expression.
Effects of treadmill running with different intensity on rat subchondral bone
Authors: Li Zhe , Liu Sheng-Yao , Xu Lei , Xu Shao-Yong , Ni Guo-Xin
Published: May 2017

Subchondral bone (SB) is recognized as a key factor in normal joint protection, not only does it provide a shock absorbing and supportive function for the cartilage, but it may also be important for cartilage metabolism. Mechanical loading is considered to be a critical regulator of skeletal homeostasis, including bone and cartilage. It is suggested that both cartilage and bone may respond to mechanical loading in an intensity-dependent manner. In this report, we have discovered that the subchondral plate became thicker with higher bone mineral density (BMD) and lower porosity, while trabecular bone became more plate-like and denser with higher BMD in high-intensity running (HIR) group. Further, HIR led to highly remodeled, less mineralized, and stiffer subchondral plate and trabecular bone. On the contrary, low-intensity running and moderate-intensity running failed to result in considerable changes in microstructure, composition and hardness. Our findings suggested that running affects SB in an intensity-dependent manner. In addition, HIR may induce change in organization and composition of SB, and consequently alter its mechanical properties. HIR-induced “brittle and stiff” SB may adversely affect the overlying articular cartilage.
A gas sensor array for the simultaneous detection of multiple VOCs
Authors: Zhang Yumin , Zhao Jianhong , Du Tengfei , Zhu Zhongqi , Zhang Jin , Liu Qingju
Published: May 2017

Air quality around the globe is declining and public health is seriously threatened by indoor air pollution. Typically, indoor air pollutants are composed of a series of volatile organic compounds (VOCs) that are generally harmful to the human body, especially VOCs with low molecular weights (less than 100 Da). Moreover, in some situations, more than one type of VOC is present; thus, a device that can detect one or more VOCs simultaneously would be most beneficial. Here, we synthesized a sensor array with 4 units to detect 4 VOCs: acetone (unit 1), benzene (unit 2), methanol (unit 3) and formaldehyde (unit 4) simultaneously. All units were simultaneously exposed to 2.5 ppm of all four VOCs. The sensitivity of unit 1 was 14.67 for acetone and less than 2.54 for the other VOCs. The sensitivities of units 2, 3 and 4 to benzene, methanol and formaldehyde were 2 18.64, 20.98 and 17.26, respectively, and less than 4.01 for the other VOCs. These results indicated that the sensor array exhibited good selectivity and could be used for the real-time monitoring of indoor air quality. Thus, this device will be useful in situations requiring the simultaneous detection of multiple VOCs.
Favorable Response to Long-term Nucleos(t)ide Analogue Therapy in HBeAg-positive Patients with High Serum Fucosyl-Agalactosyl IgG
Authors: Ho Cheng-Hsun , Tsai Hung-Wen , Lee Chen-Yeh , Huang Li-Juan , Chien Rong-Nan , Wu I-Chin , Chiu Yen-Cheng , Liu Wen-Chun , Cheng Pin-Nan , Chang Ting-Tsung , Chen Shu-Hui
Published: May 2017

Aberrant IgG glycosylation is a feature of hepatitis B virus (HBV) infection but its effect on a long-term efficacy of antiviral therapy has never been addressed. After a screening of 1,085 patients, 132 eligible HBV e antigen (HBeAg)-positive and 101 HBeAg-negative patients with anti-HBV nucleos(t)ide analogue monotherapy were enrolled with on-treatment follow-ups for at least one year. IgG1 N-glycome was profiled using mass spectrometry and evaluated for its relevance in treatment responses. The results indicated that a high level of serum fucosyl-agalactosyl IgG1 (IgG1-G0F) at baseline was associated with the severity of liver inflammation and damage but advanced treatment responses, including HBV DNA loss, HBeAg seroconversion, a reduced drug resistance rate, and a liver histological improvement at year 1, thereby improving the long-term treatment efficacy and the probability of treatment discontinuation in HBeAg-positive patients. Stepwise Cox regression analyses revealed that baseline IgG1-G0F >30% was an independent factor that links to virological response (HR 3.071, 95% CI 1.835–5.141, P < 0.001) or HBeAg seroconversion (HR 2.034, 95% CI 1.011–4.093, P = 0.046). Furthermore, a high IgG1-G0F level at the treatment endpoint was associated with an off-treatment sustained virological response. In conclusion, IgG1-G0F favors the medication outcome for HBeAg-positive chronic hepatitis B.
Acquisition of virulence factors in livestock-associated MRSA: Lysogenic conversion of CC398 strains by virulence gene-containing phages
Authors: Kraushaar Britta , Hammerl Jens Andre , Kienöl Marina , Heinig Marie Luise , Sperling Nina , Dinh Thanh Mai , Reetz Jochen , Jäckel Claudia , Fetsch Alexandra , Hertwig Stefan
Published: May 2017

Staphylococcus aureus MRSA strains belonging to the clonal complex 398 (CC398) are highly prevalent in livestock and companion animals but may also cause serious infections in humans. CC398 strains in livestock usually do not possess well-known virulence factors that can be frequently found in other MRSA sequence types (ST). Since many staphylococcal virulence genes are residing on the genomes of temperate phages, the question arises why livestock-associated (LA-) CC398 strains are only rarely infected by those phages. We isolated and characterized four temperate phages (P240, P282, P630 and P1105) containing genes of the immune evasion cluster (IEC) and/or for the Panton-Valentine leucocidin (PVL). Sequence analysis of the phage genomes showed that they are closely related to known phages and that the DNA region encoding lysis proteins, virulence factors and the integrase exhibits numerous DNA repeats which may facilitate genomic rearrangements. All phages lysed and lysogenized LA-CC398 strains. Integration of IEC phage P282 was detected at ten sites of the hosts’ chromosome. The prophages were stably inherited in LA-CC398 and enterotoxin A, staphylokinase and PVL toxin were produced. The data demonstrate that lysogenic conversion of LA-CC398 strains by virulence-associated phages may occur and that new pathotypes may emerge by this mechanism.
Hybrid Organic Tandem Solar Cell Comprising Small-Molecule Bottom and Polymer:Fullerene Top Subcells Fabricated by Thin-Film Transfer
Authors: Ka Yoonseok , Hwang Hyejin , Kim Changsoon
Published: May 2017

Multilayer structures involving solution-deposited polymer films are difficult to fabricate, not allowing for unrestricted designs of polymer-based optoelectronic devices required for maximizing their performance. Here, we fabricate a hybrid organic tandem solar cell whose top and bottom subcells have polymer:fullerene and small molecules active layers, respectively, by a solvent-free process based on transferring the polymer:fullerene layer from an elastomeric stamp onto a vacuum-deposited bottom subcell. The interface between small-molecule and transferred polymer:fullerene layers is void-free at the nanoscale, allowing for efficient charge transport across the interface. Consequently, the transfer-fabricated tandem cell has an open-circuit voltage (VOC) almost identical to the sum of VOC values for the single-junction devices. The short-circuit current density (JSC) of the tandem cell is maximized by current matching achieved by varying the thickness of the small-molecule active layer in the bottom subcell, which is verified by numerical simulations. The optimized transfer-fabricated tandem cell, whose active layers are composed of poly[2,1,3-benzothiadiazole-4,7-diyl[4,4-bis(2-ethylhexyl)-4H-cyclopenta[2,1-b:3,4-b′]dithiophene-2,6-diyl]]:[6,6]-Phenyl-C71-butyric acid methyl ester and Di-[4-(N,N-di-p-tolyl-amino)-phenyl]cyclohexane:C70, has VOC = 1.46 V, JSC = 8.48 mA/cm2, a fill factor of 0.51, leading to the power-conversion efficiency of 6.26%, the highest among small molecule–polymer:fullerene hybrid tandem solar cells demonstrated so far.
Prognostic value of hypoalbuminemia for adverse outcomes in patients with rheumatic heart disease undergoing valve replacement surgery
Authors: Wei Xue-biao , Jiang Lei , Liu Yuan-hui , Feng Du , He Peng-cheng , Chen Ji-yan , Yu Dan-qing , Tan Ning
Published: May 2017

High-risk patients with rheumatic heart disease (RHD) who were undergoing valve replacement surgery (VRS) were not identified entirely. This study included 1782 consecutive patients with RHD who were undergoing VRS to explore the relationship between hypoalbuminemia and adverse outcomes and to confirm whether hypoalbuminemia plays a role in risk evaluation. A total of 27.3% of the RHD patients had hypoalbuminemia. In-hospital deaths were significantly higher in the hypoalbuminemic group than in the non-hypoalbuminemic group (6.6% vs 3.1%, P = 0.001). Hypoalbuminemia was an independent predictor of in-hospital death (OR = 1.89, P = 0.014), even after adjusting for the Euro score. The addition of hypoalbuminemia to Euro score enhanced net reclassification improvement (0.346 for in-hospital death, P = 0.004; 0.306 for 1-year death, p = 0.005). A Kaplan-Meier curve analysis revealed that the cumulative rate of 1-year mortality after the operation was higher in patients with a new Euro score ≥6. These findings indicated that hypoalbuminemia was an independent risk factor for in-hospital and 1-year mortality after VRS in patients with RHD, which might have additive prognostic value to Euro score.
Adamdec1, Ednrb and Ptgs1/Cox1, inflammation genes upregulated in the intestinal mucosa of obese rats, are downregulated by three probiotic strains
Authors: Plaza-Díaz Julio , Robles-Sánchez Cándido , Abadía-Molina Francisco , Morón-Calvente Virginia , Sáez-Lara María José , Ruiz-Bravo Alfonso , Jiménez-Valera María , Gil Ángel , Gómez-Llorente Carolina , Fontana Luis
Published: May 2017

We have previously reported that administration of Lactobacillus paracasei CNCM I-4034, Bifidobacterium breve CNCM I-4035 and Lactobacillus rhamnosus CNCM I-4036 to obese Zucker-Lepr
fa/fa
rats attenuates liver steatosis and exerts anti-inflammatory effects. The goal of the present work was to investigate the modulation of gene expression in intestinal mucosa samples of obese Zucker-Lepr
fa/fa
rats fed the probiotic strains using a DNA microarray and postgenomic techniques. We also measured secretory IgA content in the gut and lipopolysaccharide (LPS)-binding protein (LBP) in serum. Expression of three genes (Adamdec1, Ednrb and Ptgs1/Cox1) was up-regulated in the intestinal mucosa of the obese rats compared with that in the rats when they were still lean. Probiotic administration down-regulated expression of Adamdec1 and Ednrb at the mRNA and protein levels and that of Ptgs1/Cox1 at the mRNA level, and this effect was in part mediated by a decrease in both macrophage and dendritic cell populations. Probiotic treatment also increased secretory IgA content and diminished the LBP concentration. Based on results reported in this work and else where, we propose a possible mechanism of action for these bacterial strains.
Chlamydia trachomatis infection of human endometrial stromal cells induces defective decidualisation and chemokine release
Authors: Giakoumelou Sevi , Wheelhouse Nick , Brown Jeremy , Wade Jean , Simitsidellis Ioannis , Gibson Douglas , Saunders Philippa T. K. , Horner Patrick , Entrican Gary , Howie Sarah E. M. , Horne Andrew W.
Published: May 2017

Miscarriage affects ~20% of pregnancies and maternal infections account for ~15% of early miscarriages. Chlamydia trachomatis (Ct) has been associated with miscarriage but the underlying mechanisms are unknown. Successful implantation requires endometrial stromal cell (ESC) decidualisation. Maintenance of pregnancy requires angiogenesis, establishment of the correct cellular milieu and trophoblast invasion, all of which involve the action of chemokines. Our objective was to determine whether Ct infection impacts upon ESC decidualisation and chemokine secretion. Human primary ESC were decidualised in-vitro, infected with Ct serovar E, and changes in expression of genes of interest were measured using RT-PCR, proteomic array and ELISA. We demonstrate for the first time that Ct can infect and proliferate in ESC. Expression of the decidualisation marker prolactin was decreased in Ct-infected ESC at both mRNA and protein levels. Ct infection altered the chemokine profile of decidualised ESC as shown by proteomic array. Chemokines CXCL12 and CXCL16, important for trophoblast invasion, were analysed further and expression was reduced in infected decidualised cells at mRNA and protein levels. Our data indicate that Ct infection of ESC impairs decidualisation and alters chemokine release. These findings at least partially explain how Ct infection could result in adverse pregnancy outcomes.
Trends and Outcomes of Surgical Treatment for Colorectal Cancer between 2004 and 2012- an Analysis using National Inpatient Database
Authors: Lee Meng-Tse Gabriel , Chiu Chong-Chi , Wang Chia-Chun , Chang Chia-Na , Lee Shih-Hao , Lee Matthew , Hsu Tzu-Chun , Lee Chien-Chang
Published: May 2017

Limited data are available for the epidemiology and outcome of colorectal cancer in relation to the three main surgical treatment modalities (open, laparoscopic and robotic). Using the US National Inpatient Sample database from 2004 to 2012, we identified 1,265,684 hospitalized colorectal cancer patients. Over the 9 year period, there was a 13.5% decrease in the number of hospital admissions and a 43.5% decrease in in-hospital mortality. Comparing the trend of surgical modalities, there was a 35.4% decrease in open surgeries, a 3.5 fold increase in laparoscopic surgeries, and a 41.3 fold increase in robotic surgeries. Nonetheless, in 2012, open surgery still remained the preferred surgical treatment modality (65.4%), followed by laparoscopic (31.2%) and robotic surgeries (3.4%). Laparoscopic and robotic surgeries were associated with lower in-hospital mortality, fewer complications, and shorter length of stays, which might be explained by the elective nature of surgery and earlier tumor grades. After excluding patients with advanced tumor grades, laparoscopic surgery was still associated with better outcomes and lower costs than open surgery. On the contrary, robotic surgery was associated with the highest costs, without substantial outcome benefits over laparoscopic surgery. More studies are required to clarify the cost-effectiveness of robotic surgery.