bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular probes reveal deviations from Amontons’ law in multi-asperity frictional contacts
Authors: Weber B. , Suhina T. , Junge T. , Pastewka L. , Brouwer A. M. , Bonn D. 
Published: February 2018

AbstractAmontons’ law defines the friction coefficient as the ratio between friction force and normal force, and assumes that both these forces depend linearly on the real contact area between the two sliding surfaces. However, experimental testing of frictional contact models has proven difficult, because few in situ experiments are able to resolve this real contact area. Here, we present a contact detection method with molecular-level sensitivity. We find that while the friction force is proportional to the real contact area, the real contact area does not increase linearly with normal force. Contact simulations show that this is due to both elastic interactions between asperities on the surface and contact plasticity of the asperities. We reproduce the contact area and fine details of the measured contact geometry by including plastic hardening into the simulations. These new insights will pave the way for a quantitative microscopic understanding of contact mechanics and tribology.
Early circulating tumor DNA dynamics and clonal selection with palbociclib and fulvestrant for breast cancer
Authors: O’Leary Ben , Hrebien Sarah , Morden James P. , Beaney Matthew , Fribbens Charlotte , Huang Xin , Liu Yuan , Bartlett Cynthia Huang , Koehler Maria , Cristofanilli Massimo , Garcia-Murillas Isaac , Bliss Judith M. , Turner Nicholas C. 
Published: February 2018

AbstractCDK4/6 inhibition substantially improves progression-free survival (PFS) for women with advanced estrogen receptor-positive breast cancer, although there are no predictive biomarkers. Early changes in circulating tumor DNA (ctDNA) level may provide early response prediction, but the impact of tumor heterogeneity is unknown. Here we use plasma samples from patients in the randomized phase III PALOMA-3 study of CDK4/6 inhibitor palbociclib and fulvestrant for women with advanced breast cancer and show that relative change in PIK3CA ctDNA level after 15 days treatment strongly predicts PFS on palbociclib and fulvestrant (hazard ratio 3.94, log-rank p = 0.0013). ESR1 mutations selected by prior hormone therapy are shown to be frequently sub clonal, with ESR1 ctDNA dynamics offering limited prediction of clinical outcome. These results suggest that early ctDNA dynamics may provide a robust biomarker for CDK4/6 inhibitors, with early ctDNA dynamics demonstrating divergent response of tumor sub clones to treatment.
Elongator and codon bias regulate protein levels in mammalian peripheral neurons
Authors: Goffena Joy , Lefcort Frances , Zhang Yongqing , Lehrmann Elin , Chaverra Marta , Felig Jehremy , Walters Joseph , Buksch Richard , Becker Kevin G. , George Lynn 
Published: February 2018

AbstractFamilial dysautonomia (FD) results from mutation in IKBKAP/ELP1, a gene encoding the scaffolding protein for the Elongator complex. This highly conserved complex is required for the translation of codon-biased genes in lower organisms. Here we investigate whether Elongator serves a similar function in mammalian peripheral neurons, the population devastated in FD. Using codon-biased eGFP sensors, and multiplexing of codon usage with transcriptome and proteome analyses of over 6,000 genes, we identify two categories of genes, as well as specific gene identities that depend on Elongator for normal expression. Moreover, we show that multiple genes in the DNA damage repair pathway are codon-biased, and that with Elongator loss, their misregulation is correlated with elevated levels of DNA damage. These findings link Elongator’s function in the translation of codon-biased genes with both the developmental and neurodegenerative phenotypes of FD, and also clarify the increased risk of cancer associated with the disease.
Whole-exome sequencing reveals the origin and evolution of hepato-cholangiocarcinoma
Authors: Wang Anqiang , Wu Liangcai , Lin Jianzhen , Han Longzhe , Bian Jin , Wu Yan , Robson Simon C. , Xue Lai , Ge Yunxia , Sang Xinting , Wang Wenze , Zhao Haitao 
Published: February 2018

AbstractHepatocellular-cholangiocarcinoma (H-ChC) is a rare subtype of liver cancer with clinicopathological features of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). To date, molecular mechanisms underlying the co-existence of HCC and iCCA components in a single tumor remain elusive. Here, we show that H-ChC samples contain substantial private mutations from WES analyses, ranging from 33.1 to 86.4%, indicative of substantive intratumor heterogeneity (ITH). However, on the other hand, numerous ubiquitous mutations shared by HCC and iCCA suggest the monoclonal origin of H-ChC. Mutated genes identified herein, e.g., VCAN, ACVR2A, and FCGBP, are speculated to contribute to distinct differentiation of HCC and iCCA within H-ChC. Moreover, immunohistochemistry demonstrates that EpCAM is highly expressed in 80% of H-ChC, implying the stemness of such liver cancer. In summary, our data highlight the monoclonal origin and stemness of H-ChC, as well as substantial intratumoral heterogeneity.
TET-mediated epimutagenesis of the Arabidopsis thaliana methylome
Authors: Ji Lexiang , Jordan William T. , Shi Xiuling , Hu Lulu , He Chuan , Schmitz Robert J. 
Published: February 2018

AbstractDNA methylation in the promoters of plant genes sometimes leads to transcriptional repression, and the loss of DNA methylation in methyltransferase mutants results in altered gene expression and severe developmental defects. However, many cases of naturally occurring DNA methylation variations have been reported, whereby altered expression of differentially methylated genes is responsible for agronomically important traits. The ability to manipulate plant methylomes to generate epigenetically distinct individuals could be invaluable for breeding and research purposes. Here, we describe “epimutagenesis,” a method to rapidly generate DNA methylation variation through random demethylation of the Arabidopsis thaliana genome. This method involves the expression of a human ten–eleven translocation (TET) enzyme, and results in widespread hypomethylation that can be inherited to subsequent generations, mimicking mutants in the maintenance of DNA methyltransferase met1. Application of epimutagenesis to agriculturally significant plants may result in differential expression of alleles normally silenced by DNA methylation, uncovering previously hidden phenotypic variations.
High field charge order across the phase diagram of YBa2Cu3Oy
Authors: Laliberté Francis , Frachet Mehdi , Benhabib Siham , Borgnic Benjamin , Loew Toshinao , Porras Juan , Le Tacon Mathieu , Keimer Bernhard , Wiedmann Steffen , Proust Cyril , LeBoeuf David 
Published: February 2018

AbstractIn hole-doped cuprates there is now compelling evidence that inside the pseudogap phase, charge order breaks translational symmetry. In YBa2Cu3O
y
charge order emerges in two steps: a 2D order found at zero field and at high temperature inside the pseudogap phase, and a 3D order that is superimposed below the superconducting transition Tc when superconductivity is weakened by a magnetic field. Several issues still need to be addressed such as the effect of disorder, the relationship between those charge orders and their respective impact on the Fermi surface. Here, we report high magnetic field sound velocity measurements of the 3D charge order in underdoped YBa2Cu3O
y
in a large doping range. We found that the 3D charge order exists over the same doping range as its 2D counterpart, indicating an intimate connection between the two distinct orders. Moreover, our data suggest that 3D charge order has only a limited impact on low-lying electronic states of YBa2Cu3O
y
.
Exogenous hydrogen sulfide gas does not induce hypothermia in normoxic mice
Authors: Hemelrijk Sebastiaan D. , Dirkes Marcel C. , van Velzen Marit H. N. , Bezemer Rick , van Gulik Thomas M. , Heger Michal 
Published: February 2018

AbstractHydrogen sulfide (H2S, 80 ppm) gas in an atmosphere of 17.5% oxygen reportedly induces suspended animation in mice; a state analogous to hibernation that entails hypothermia and hypometabolism. However, exogenous H2S in combination with 17.5% oxygen is able to induce hypoxia, which in itself is a trigger of hypometabolism/hypothermia. Using non-invasive thermographic imaging, we demonstrated that mice exposed to hypoxia (5% oxygen) reduce their body temperature to ambient temperature. In contrast, animals exposed to 80 ppm H2S under normoxic conditions did not exhibit a reduction in body temperature compared to normoxic controls. In conclusion, mice induce hypothermia in response to hypoxia but not H2S gas, which contradicts the reported findings and putative contentions.
Fatty Acid Supplementation Reverses the Small Colony Variant Phenotype in Triclosan-Adapted Staphylococcus aureus: Genetic, Proteomic and Phenotypic Analyses
Authors: Bazaid Abdulrahman S. , Forbes Sarah , Humphreys Gavin J. , Ledder Ruth G. , O’Cualain Ronan , McBain Andrew J. 
Published: February 2018

AbstractStaphylococcus aureus can develop a small colony variant (SCV) phenotype in response to sub-lethal exposure to the biocide triclosan. In the current study, whole genome sequencing was performed and changes in virulence were investigated in five Staphylococcus aureus strains following repeated exposure to triclosan. Following exposure, 4/5 formed SCV and exhibited point mutations in the triclosan target gene fabI with 2/4 SCVs showing mutations in both fabI and fabD. The SCV phenotype was in all cases immediately reversed by nutritional supplementation with fatty acids or by repeated growth in the absence of triclosan, although fabI mutations persisted in 3/4 reverted SCVs. Virulence, determined using keratinocyte invasion and Galleria mellonella pathogenicity assays was significantly (p < 0.05) attenuated in 3/4 SCVs and in the non-SCV triclosan-adapted bacterium. Proteomic analysis revealed elevated FabI in 2/3 SCV and down-regulation in a protein associated with virulence in 1/3 SCV. In summary, attenuated keratinocyte invasion and larval virulence in triclosan-induced SCVs was associated with decreases in growth rate and virulence factor expression. Mutation occurred in fabI, which encodes the main triclosan target in all SCVs and the phenotype was reversed by fatty acid supplementation, demonstrating an association between fatty acid metabolism and triclosan-induced SCV.
Recognition motif and mechanism of ripening inhibitory peptides in plant hormone receptor ETR1
Authors: Milić Dalibor , Dick Markus , Mulnaes Daniel , Pfleger Christopher , Kinnen Anna , Gohlke Holger , Groth Georg 
Published: February 2018

AbstractSynthetic peptides derived from ethylene-insensitive protein 2 (EIN2), a central regulator of ethylene signalling, were recently shown to delay fruit ripening by interrupting protein–protein interactions in the ethylene signalling pathway. Here, we show that the inhibitory peptide NOP-1 binds to the GAF domain of ETR1 – the prototype of the plant ethylene receptor family. Site-directed mutagenesis and computational studies reveal the peptide interaction site and a plausible molecular mechanism for the ripening inhibition.
Metabolic characterization of directly reprogrammed renal tubular epithelial cells (iRECs)
Authors: Lagies Simon , Pichler Roman , Kaminski Michael M. , Schlimpert Manuel , Walz Gerd , Lienkamp Soeren S. , Kammerer Bernd 
Published: February 2018

AbstractFibroblasts can be directly reprogrammed to induced renal tubular epithelial cells (iRECs) using four transcription factors. These engineered cells may be used for disease modeling, cell replacement therapy or drug and toxicity testing. Direct reprogramming induces drastic changes in the transcriptional landscape, protein expression, morphological and functional properties of cells. However, how the metabolome is changed by reprogramming and to what degree it resembles the target cell type remains unknown. Using untargeted gas chromatography-mass spectrometry (GC-MS) and targeted liquid chromatography-MS, we characterized the metabolome of mouse embryonic fibroblasts (MEFs), iRECs, mIMCD-3 cells, and whole kidneys. Metabolic fingerprinting can distinguish each cell type reliably, revealing iRECs are most similar to mIMCD-3 cells and clearly separate from MEFs used for reprogramming. Treatment with the cytotoxic drug cisplatin induced typical changes in the metabolic profile of iRECs commonly occurring in acute renal injury. Interestingly, metabolites in the medium of iRECs, but not of mIMCD-3 cells or fibroblast could distinguish treated and non-treated cells by cluster analysis. In conclusion, direct reprogramming of fibroblasts into renal tubular epithelial cells strongly influences the metabolome of engineered cells, suggesting that metabolic profiling may aid in establishing iRECs as in vitro models for nephrotoxicity testing in the future.
The energy sensor OsSnRK1a confers broad-spectrum disease resistance in rice
Authors: Filipe Osvaldo , De Vleesschauwer David , Haeck Ashley , Demeestere Kristof , Höfte Monica 
Published: February 2018

AbstractSucrose non-fermenting-1-related protein kinase-1 (SnRK1) belongs to a family of evolutionary conserved kinases with orthologs in all eukaryotes, ranging from yeasts (SnF1) to mammals (AMP-Activated kinase). These kinases sense energy deficits caused by nutrient limitation or stress and coordinate the required adaptations to maintain energy homeostasis and survival. In plants, SnRK1 is a global regulator of plant metabolism and is also involved in abiotic stress responses. Its role in the response to biotic stress, however, is only starting to be uncovered. Here we studied the effect of altered SnRK1a expression on growth and plant defense in rice. OsSnRK1a overexpression interfered with normal growth and development and increased resistance against both (hemi)biotrophic and necrotrophic pathogens, while OsSnRK1a silencing in RNAi lines increased susceptibility. OsSnRK1a overexpression positively affected the salicylic acid pathway and boosted the jasmonate-mediated defense response after inoculation with the blast fungus Pyricularia oryzae. Together these findings strongly suggest OsSnRK1a to be involved in plant basal immunity and favor a model whereby OsSnRK1a acts as a master switch that regulates growth-immunity trade-offs.
Fat accretion measurements strengthen the relationship between feed conversion efficiency and Nitrogen isotopic discrimination while rumen microbial genes contribute little
Authors: Meale Sarah J. , Auffret Marc D. , Watson Mick , Morgavi Diego P. , Cantalapiedra-Hijar Gonzalo , Duthie Carol-Anne , Roehe Rainer , Dewhurst Richard J. 
Published: February 2018

AbstractThe use of biomarkers for feed conversion efficiency (FCE), such as Nitrogen isotopic discrimination (Δ15N), facilitates easier measurement and may be useful in breeding strategies. However, we need to better understand the relationship between FCE and Δ15N, particularly the effects of differences in the composition of liveweight gain and rumen N metabolism. Alongside measurements of FCE and Δ15N, we estimated changes in body composition and used dietary treatments with and without nitrates, and rumen metagenomics to explore these effects. Nitrate fed steers had reduced FCE and higher Δ15N in plasma compared to steers offered non-nitrate containing diets. The negative relationship between FCE and Δ15N was strengthened with the inclusion of fat depth change at the 3rdlumbar vertebrae, but not with average daily gain. We identified 1,700 microbial genes with a relative abundance >0.01% of which, 26 were associated with Δ15N. These genes explained 69% of variation in Δ15N and showed clustering in two distinct functional networks. However, there was no clear relationship between their relative abundances and Δ15N, suggesting that rumen microbial genes contribute little to Δ15N. Conversely, we show that changes in the composition of gain (fat accretion) provide additional strength to the relationship between FCE and Δ15N.
Vacancy assisted He-interstitial clustering and their elemental interaction at fcc-bcc semicoherent metallic interface
Authors: Saikia Ujjal , Sahariah Munima B. , González César , Pandey Ravindra 
Published: February 2018

AbstractCu-Nb layered nanocomposite system can be considered as a prototype system to investigate stability of the fcc-bcc semicoherent metallic interfaces. Theoretical simulations based on density functional theory have been performed in order to investigate the stability of different defects in such interfaces. The calculations find the interfacial misfit dislocation intersections as the preferred site for defects including a vacancy, He-interstitial, and a vacancy-He complex in good agreement with previous works. Our results suggest that the presence of a metallic vacancy may act as a sink for defect and favour the migration of He interstitials leading to their aggregation at the interface. The potential capability of the vacancy to accommodate He atoms was also predicted with a higher affinity towards Nb. This aggregation of He atoms is driven by local density of electron and strain in a region in the neighbourhood of Nb. Finally, we propose a plausible picture of defect energetics in the vicinity of the interface based on the Voronoi volume and Bader’s charge analysis. This analysis may replace the conventional methods used for surface energetics mapping which are extremely tedious for such large systems.
PDE4D regulates Spine Plasticity and Memory in the Retrosplenial Cortex
Authors: Baumgärtel Karsten , Green Andrea , Hornberger Diana , Lapira Jennifer , Rex Christopher , Wheeler Damian G. , Peters Marco 
Published: February 2018

AbstractThe retrosplenial cortex (RSC) plays a critical role in episodic memory, but the molecular mechanisms governing plasticity in this structure are poorly understood. Diverse studies have demonstrated a role for RSC in acquisition, early consolidation and retrieval similar to the hippocampus (HC), as well as in systems consolidation similar to the anterior cingulate cortex. Here, we asked whether established molecular and structural substrates of memory consolidation in the HC also engage in RSC shortly after learning. We show striking parallels in training induced gene-activation in HC and RSC following contextual conditioning, which is blocked by systemic administration of an NMDA receptor antagonist. Long-term memory is enhanced by retrosplenial and hippocampal knockdown (KD) of the cAMP specific phosphodiesterase Pde4d. However, while training per se induces lasting spine changes in HC, this does not occur in RSC. Instead, increases in the number of mature dendritic spines are found in the RSC only if cAMP signaling is augmented by Pde4d KD, and spine changes are at least partially independent of training. This research highlights parallels and differences in spine plasticity mechanisms between HC and RSC, and provides evidence for a functional dissociation of the two.
One-step fabrication of robust superhydrophobic and superoleophilic surfaces with self-cleaning and oil/water separation function
Authors: Zhang Zhi-hui , Wang Hu-jun , Liang Yun-hong , Li Xiu-juan , Ren Lu-quan , Cui Zhen-quan , Luo Cheng 
Published: February 2018

AbstractSuperhydrophobic surfaces have great potential for application in self-cleaning and oil/water separation. However, the large-scale practical applications of superhydrophobic coating surfaces are impeded by many factors, such as complicated fabrication processes, the use of fluorinated reagents and noxious organic solvents and poor mechanical stability. Herein, we describe the successful preparation of a fluorine-free multifunctional coating without noxious organic solvents that was brushed, dipped or sprayed onto glass slides and stainless-steel meshes as substrates. The obtained multifunctional superhydrophobic and superoleophilic surfaces (MSHOs) demonstrated self-cleaning abilities even when contaminated with or immersed in oil. The superhydrophobic surfaces were robust and maintained their water repellency after being scratched with a knife or abraded with sandpaper for 50 cycles. In addition, stainless-steel meshes sprayed with the coating quickly separated various oil/water mixtures with a high separation efficiency (>93%). Furthermore, the coated mesh maintained a high separation efficiency above 95% over 20 cycles of separation. This simple and effective strategy will inspire the large-scale fabrication of multifunctional surfaces for practical applications in self-cleaning and oil/water separation.
Association between homocysteine and conventional predisposing factors on risk of stroke in patients with hypertension
Authors: Pang Hui , Han Bing , Fu Qiang , Hao Lin , Zong Zhenkun 
Published: February 2018

AbstractPrevious studies have focused mostly on independent effects of the stroke risk factors, whereas little attention has been paid to interactions between individual factors which may be important for stroke prevention. We collected data related to the patients’ demographic characteristics, history of chronic diseases and lifestyle factors in 2258 patients with primary hypertension. Logistic regression models based on odds ratio (OR) with their associated 95% confidence interval (CI) were used to estimate an independent effect of homocysteine (Hcy) on the risk of stroke but also include the interactions between Hcy and other risk factors. Hcy was associated with an increased OR of the risk of stroke in both hypertension patients (OR, 1.027; 95% CI, 1.016–1.038; P < 0.001) and H-type hypertension patients (OR, 1.026; 95% CI, 1.014–1.037; P < 0.001), after adjustment for potential confounding factors. Among the hypertension participants, three tests of interactions between Hcy and other risk factors were statistically significant: sex, systolic blood pressure and diastolic blood pressure. In conclusion, complexities of the interactions of Hcy stratified by sex and blood pressure need to be considered in predicting overall risk and selecting certain treatments for stroke prevention.
Towards spontaneous parametric down conversion from monolayer MoS2
Authors: Dinparasti Saleh Hatef , Vezzoli Stefano , Caspani Lucia , Branny Artur , Kumar Santosh , Gerardot Brian D. , Faccio Daniele 
Published: February 2018

AbstractWe present a detailed study of the second order nonlinearity of 2D (mono-atomic layer) dichalcogenide MoS2, both in the visible and in the IR regime, and test its potential for spontaneous parametric down-conversion (SPDC), the amplification of vacuum fluctuations mediated by optical nonlinearity. We develop a model of SPDC from a deeply subwavelength nonlinear medium, where phase matching conditions are completely relaxed, and make predictions about the rate of emitted photons, their momentum, polarisation and spectrum. We show that detection in the visible spectral region is hindered by the strong photoluminescence background. Moving to the IR regime we observe indications of SPDC by performing polarization, power dependence and lifetime measurements around 1560 nm. We show that the signal from a single monolayer is qualitatively different from that generated by multi-layer MoS2. Finally, we characterize the latter as a new kind of photo-luminescence emission which is enhanced at the edges of multi-layer MoS2.