bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tight cohesion between glycolipid membranes results from balanced water–headgroup interactions
Authors: Kanduč Matej , Schlaich Alexander , de Vries Alex H. , Jouhet Juliette , Maréchal Eric , Demé Bruno , Netz Roland R. , Schneck Emanuel 
Published: April 2017

AbstractMembrane systems that naturally occur as densely packed membrane stacks contain high amounts of glycolipids whose saccharide headgroups display multiple small electric dipoles in the form of hydroxyl groups. Experimentally, the hydration repulsion between glycolipid membranes is of much shorter range than that between zwitterionic phospholipids whose headgroups are dominated by a single large dipole. Using solvent-explicit molecular dynamics simulations, here we reproduce the experimentally observed, different pressure-versus-distance curves of phospholipid and glycolipid membrane stacks and show that the water uptake into the latter is solely driven by the hydrogen bond balance involved in non-ideal water/sugar mixing. Water structuring effects and lipid configurational perturbations, responsible for the longer-range repulsion between phospholipid membranes, are inoperative for the glycolipids. Our results explain the tight cohesion between glycolipid membranes at their swelling limit, which we here determine by neutron diffraction, and their unique interaction characteristics, which are essential for the biogenesis of photosynthetic membranes.
Diurnal and seasonal molecular rhythms in human neocortex and their relation to Alzheimer’s disease
Authors: Lim Andrew S. P. , Klein Hans-Ulrich , Yu Lei , Chibnik Lori B. , Ali Sanam , Xu Jishu , Bennett David A. , De Jager Philip L. 
Published: April 2017

AbstractCircadian and seasonal rhythms are seen in many species, modulate several aspects of human physiology, including brain functions such as mood and cognition, and influence many neurological and psychiatric illnesses. However, there are few data regarding the genome-scale molecular correlates underlying these rhythms, especially in the human brain. Here, we report widespread, site-specific and interrelated diurnal and seasonal rhythms of gene expression in the human brain, and show their relationship with parallel rhythms of epigenetic modification including histone acetylation, and DNA methylation. We also identify transcription factor-binding sites that may drive these effects. Further, we demonstrate that Alzheimer’s disease pathology disrupts these rhythms. These data suggest that interrelated diurnal and seasonal epigenetic and transcriptional rhythms may be an important feature of human brain biology, and perhaps human biology more broadly, and that changes in such rhythms may be consequences of, or contributors to, diseases such as Alzheimer’s disease.
Macrocycle peptides delineate locked-open inhibition mechanism for microorganism phosphoglycerate mutases
Authors: Yu Hao , Dranchak Patricia , Li Zhiru , MacArthur Ryan , Munson Matthew S. , Mehzabeen Nurjahan , Baird Nathan J. , Battalie Kevin P. , Ross David , Lovell Scott , Carlow Clotilde K. S. , Suga Hiroaki , Inglese James 
Published: April 2017

AbstractGlycolytic interconversion of phosphoglycerate isomers is catalysed in numerous pathogenic microorganisms by a cofactor-independent mutase (iPGM) structurally distinct from the mammalian cofactor-dependent (dPGM) isozyme. The iPGM active site dynamically assembles through substrate-triggered movement of phosphatase and transferase domains creating a solvent inaccessible cavity. Here we identify alternate ligand binding regions using nematode iPGM to select and enrich lariat-like ligands from an mRNA-display macrocyclic peptide library containing >1012 members. Functional analysis of the ligands, named ipglycermides, demonstrates sub-nanomolar inhibition of iPGM with complete selectivity over dPGM. The crystal structure of an iPGM macrocyclic peptide complex illuminated an allosteric, locked-open inhibition mechanism placing the cyclic peptide at the bi-domain interface. This binding mode aligns the pendant lariat cysteine thiolate for coordination with the iPGM transition metal ion cluster. The extended charged, hydrophilic binding surface interaction rationalizes the persistent challenges these enzymes have presented to small-molecule screening efforts highlighting the important roles of macrocyclic peptides in expanding chemical diversity for ligand discovery.
MET amplification and epithelial-to-mesenchymal transition exist as parallel resistance mechanisms in erlotinib-resistant, EGFR-mutated, NSCLC HCC827 cells
Authors: Jakobsen K R , Demuth C , Madsen A T , Hussmann D , Vad-Nielsen J , Nielsen A L , Sorensen B S 
Published: April 2017

AbstractAlthough many epidermal growth factor receptor (EGFR)-mutated lung cancer patients initially benefit from the EGFR-inhibitor erlotinib, all acquire resistance. So far, several mechanisms implicated in resistance have been identified, but the existence of multiple resistance mechanisms in parallel have only been sparsely investigated. In this study, we investigated parallel resistance mechanisms acquired by HCC827, an EGFR-mutated adenocarcinoma cell line dependent on EGFR activity and sensitive to erlotinib. The cell line was treated with erlotinib by stepwise escalation of the drug-concentration and erlotinib-resistant (HCC827ER) cells created. HCC827ER cells depicted a mixed epithelial and mesenchymal phenotype. To clarify potential parallel resistance mechanisms, 14 resistant subclones were established by limited dilution. Interestingly, all HCC827ER subclones harbored either a MET-amplification (6/14) or underwent EMT (8/14), mechanisms both found in previous studies, but not in co-occurrence. Both subclone-types were resistant to erlotinib, but only MET-subclones responded to the MET-inhibitors crizotinib and capmatinib. EMT-subclones on the other hand had markedly increased FGFR1 expression and responded to the FGFR-inhibitor AZD4547, whereas MET-subclones did not. Monitoring gene expression through the development of HCC827ER revealed upregulation of FGFR1 expression as an early response to erlotinib. In addition, FGFR1 expression increased upon short-term erlotinib treatment (48 h) identifying a physiological role immediately after erlotinib exposure. The high FGFR1 expression seen in EMT-subclones was stable even after five passages without erlotinib. Here we show, that parallel resistance mechanisms appear during erlotinib-resistance development in EGFR-mutated NSCLC cells and highlight a role for FGFR1 expression changes as an early response to erlotinib as well as a bypass-signaling mechanism.
Characterizing rare fluctuations in soft particulate flows
Authors: Rahbari S.H.E. , Saberi A.A. , Park Hyunggyu , Vollmer J. 
Published: April 2017

AbstractSoft particulate media include a wide range of systems involving athermal dissipative particles both in non-living and biological materials. Characterization of flows of particulate media is of great practical and theoretical importance. A fascinating feature of these systems is the existence of a critical rigidity transition in the dense regime dominated by highly intermittent fluctuations that severely affects the flow properties. Here, we unveil the underlying mechanisms of rare fluctuations in soft particulate flows. We find that rare fluctuations have different origins above and below the critical jamming density and become suppressed near the jamming transition. We then conjecture a time-independent local fluctuation relation, which we verify numerically, and that gives rise to an effective temperature. We discuss similarities and differences between our proposed effective temperature with the conventional kinetic temperature in the system by means of a universal scaling collapse.
Genomic and immune heterogeneity are associated with differential responses to therapy in melanoma
Authors: Reuben Alexandre , Spencer Christine N. , Prieto Peter A. , Gopalakrishnan Vancheswaran , Reddy Sangeetha M. , Miller John P. , Mao Xizeng , De Macedo Mariana Petaccia , Chen Jiong , Song Xingzhi , Jiang Hong , Chen Pei-Ling , Beird Hannah C. , Garber Haven R. , Roh Whijae , Wani Khalida , Chen Eveline , Haymaker Cara , Forget Marie-Andrée , Little Latasha D. , Gumbs Curtis , Thornton Rebecca L. , Hudgens Courtney W. , Chen Wei-Shen , Austin-Breneman Jacob , Sloane Robert Szczepaniak , Nezi Luigi , Cogdill Alexandria P. , Bernatchez Chantale , Roszik Jason , Hwu Patrick , Woodman Scott E. , Chin Lynda , Tawbi Hussein , Davies Michael A. , Gershenwald Jeffrey E. , Amaria Rodabe N. , Glitza Isabella C. , Diab Adi , Patel Sapna P. , Hu Jianhua , Lee Jeffrey E. , Grimm Elizabeth A. , Tetzlaff Michael T. , Lazar Alexander J. , Wistuba Ignacio I. , Clise-Dwyer Karen , Carter Brett W. , Zhang Jianhua , Futreal P. Andrew , Sharma Padmanee , Allison James P. , Cooper Zachary A. , Wargo Jennifer A. 
Published: April 2017

AbstractAppreciation for genomic and immune heterogeneity in cancer has grown though the relationship of these factors to treatment response has not been thoroughly elucidated. To better understand this, we studied a large cohort of melanoma patients treated with targeted therapy or immune checkpoint blockade (n = 60). Heterogeneity in therapeutic responses via radiologic assessment was observed in the majority of patients. Synchronous melanoma metastases were analyzed via deep genomic and immune profiling, and revealed substantial genomic and immune heterogeneity in all patients studied, with considerable diversity in T cell frequency, and few shared T cell clones (<8% on average) across the cohort. Variables related to treatment response were identified via these approaches and through novel radiomic assessment. These data yield insight into differential therapeutic responses to targeted therapy and immune checkpoint blockade in melanoma, and have key translational implications in the age of precision medicine.
Restoring heart function and electrical integrity: closing the circuit
Authors: Monteiro Luís Miguel , Vasques-Nóvoa Francisco , Ferreira Lino , Pinto-do-Ó Perpétua , Nascimento Diana Santos 
Published: April 2017

AbstractCardiovascular diseases are the main cause of death in the world and are often associated with the occurrence of arrhythmias due to disruption of myocardial electrical integrity. Pathologies involving dysfunction of the specialized cardiac excitatory/conductive tissue are also common and constitute an added source of morbidity and mortality since current standard therapies withstand a great number of limitations. As electrical integrity is essential for a well-functioning heart, innovative strategies have been bioengineered to improve heart conduction and/or promote myocardial repair, based on: (1) gene and/or cell delivery; or (2) conductive biomaterials as tools for cardiac tissue engineering. Herein we aim to review the state-of-art in the area, while briefly describing the biological principles underlying the heart electrical/conduction system and how this system can be disrupted in heart disease. Suggestions regarding targets for future studies are also presented.
Unique residues in the ATP gated human P2X7 receptor define a novel allosteric binding pocket for the selective antagonist AZ10606120
Authors: Allsopp Rebecca C. , Dayl Sudad , Schmid Ralf , Evans Richard J. 
Published: April 2017

AbstractThe P2X7 receptor (P2X7R) for ATP is a therapeutic target for pathophysiological states including inflammation, pain management and epilepsy. This is facilitated by the predicted low side effect profile as the high concentrations of ATP required to activate the receptor are usually only found following cell damage/disease and so P2X7Rs respond to a “danger” signal and are not normally active. AZ10606120 is a selective antagonist for P2X7Rs (IC50 of ~10 nM) and ineffective at the P2X1R (at 10 μM). To determine the molecular basis of selectivity we generated a series of P2X7/1R chimeras and mutants. Two regions that are unique to the P2X7R, a loop insertion (residues 73–79) and threonine residues T90 and T94, are required for high affinity antagonist action. Point mutations ruled out an orthosteric antagonist site. Mutations and molecular modelling identified an allosteric binding site that forms at the subunit interface at the apex of the receptor. Molecular dynamics simulations indicated that unique P2X7R features regulate access of AZ10606120 to the allosteric site. The characterisation of the allosteric pocket provides a new and novel target for rational P2X7R drug development.
Elastic Anomaly and Polyamorphic Transition in (La, Ce)-based Bulk Metallic Glass under Pressure
Authors: Qi Xintong , Zou Yongtao , Wang Xuebing , Chen Ting , Welch David O. , Jiang Jianzhong , Li Baosheng 
Published: April 2017

AbstractPressure-induced polyamorphism in Ce-based metallic glass has attracted significant interest in condensed matter physics. In this paper, we discover that in association with the polyamorphism of La32Ce32Al16Ni5Cu15 bulk metallic glass, the acoustic velocities, measured up to 12.3 GPa using ultrasonic interferometry, exhibit velocity minima at 1.8 GPa for P wave and 3.2 GPa for S wave. The low and high density amorphous states are distinguished by their distinct pressure derivatives of the bulk and shear moduli. The elasticity, permanent densification, and polyamorphic transition are interpreted by the topological rearrangement of solute-centered clusters in medium-range order (MRO) mediated by the 4f electron delocalization of Ce under pressure. The precisely measured acoustic wave travel times which were used to derive the velocities and densities provided unprecedented data to document the evolution of the bulk and shear elastic moduli associated with a polyamorphic transition in La32Ce32Al16Ni5Cu15 bulk metallic glass and can shed new light on the mechanisms of polyamorphism and structural evolution in metallic glasses under pressure.
Aqueous Solution Chemistry of Ammonium Cation in the Auger Time Window
Authors: Hollas Daniel , Pohl Marvin N. , Seidel Robert , Aziz Emad F. , Slavíček Petr , Winter Bernd 
Published: April 2017

AbstractWe report on chemical reactions triggered by core-level ionization of ammonium ($${{\rm{NH}}}_{4}^{+}$$

NH

4

+

) cation in aqueous solution. Based on a combination of photoemission experiments from a liquid microjet and high-level ab initio simulations, we identified simultaneous single and double proton transfer occurring on a very short timescale spanned by the Auger-decay lifetime. Molecular dynamics simulations indicate that the proton transfer to a neighboring water molecule leads to essentially complete formation of H3O+ (aq) and core-ionized ammonia $${({{\rm{NH}}}_{3}^{+})}^{\ast }$$

(

NH

3

+

)

⁎

(aq) within the ~7 fs lifetime of the nitrogen 1s core hole. A second proton transfer leads to a transient structure with the proton shared between the remaining NH2 moiety and another water molecule in the hydration shell. These ultrafast proton transfers are stimulated by very strong hydrogen bonds between the ammonium cation and water. Experimentally, the proton transfer dynamics is identified from an emerging signal at the high-kinetic energy side of the Auger-electron spectrum in analogy to observations made for other hydrogen-bonded aqueous solutions. The present study represents the most pronounced charge separation observed upon core ionization in liquids so far.
Nanodiamonds as multi-purpose labels for microscopy
Authors: Hemelaar S. R. , de Boer P. , Chipaux M. , Zuidema W. , Hamoh T. , Martinez F. Perona , Nagl A. , Hoogenboom J. P. , Giepmans B. N. G. , Schirhagl R. 
Published: April 2017

AbstractNanodiamonds containing fluorescent nitrogen-vacancy centers are increasingly attracting interest for use as a probe in biological microscopy. This interest stems from (i) strong resistance to photobleaching allowing prolonged fluorescence observation times; (ii) the possibility to excite fluorescence using a focused electron beam (cathodoluminescence; CL) for high-resolution localization; and (iii) the potential use for nanoscale sensing. For all these schemes, the development of versatile molecular labeling using relatively small diamonds is essential. Here, we show the direct targeting of a biological molecule with nanodiamonds as small as 70 nm using a streptavidin conjugation and standard antibody labelling approach. We also show internalization of 40 nm sized nanodiamonds. The fluorescence from the nanodiamonds survives osmium-fixation and plastic embedding making them suited for correlative light and electron microscopy. We show that CL can be observed from epon-embedded nanodiamonds, while surface-exposed nanoparticles also stand out in secondary electron (SE) signal due to the exceptionally high diamond SE yield. Finally, we demonstrate the magnetic read-out using fluorescence from diamonds prior to embedding. Thus, our results firmly establish nanodiamonds containing nitrogen-vacancy centers as unique, versatile probes for combining and correlating different types of microscopy, from fluorescence imaging and magnetometry to ultrastructural investigation using electron microscopy.
IMGMD: A platform for the integration and standardisation of In silico Microbial Genome-scale Metabolic Models
Authors: Ye Chao , Xu Nan , Dong Chuan , Ye Yuannong , Zou Xuan , Chen Xiulai , Guo Fengbiao , Liu Liming 
Published: April 2017

AbstractGenome-scale metabolic models (GSMMs) constitute a platform that combines genome sequences and detailed biochemical information to quantify microbial physiology at the system level. To improve the unity, integrity, correctness, and format of data in published GSMMs, a consensus IMGMD database was built in the LAMP (Linux + Apache + MySQL + PHP) system by integrating and standardizing 328 GSMMs constructed for 139 microorganisms. The IMGMD database can help microbial researchers download manually curated GSMMs, rapidly reconstruct standard GSMMs, design pathways, and identify metabolic targets for strategies on strain improvement. Moreover, the IMGMD database facilitates the integration of wet-lab and in silico data to gain an additional insight into microbial physiology. The IMGMD database is freely available, without any registration requirements, at http://imgmd.jiangnan.edu.cn/database.
Poynting vector analysis for wireless power transfer between magnetically coupled coils with different loads
Authors: Guo Yunsheng , Li Jiansheng , Hou Xiaojuan , Lv Xiaolong , Liang Hao , Zhou Ji , Wu Hongya 
Published: April 2017

AbstractWireless power transfer is a nonradiative type of transmission that is performed in the near-field region. In this region, the electromagnetic fields that are produced by both the transmitting and receiving coils are evanescent fields, which should not transmit energy. This then raises the question of how the energy can be transferred. Here we describe a theoretical study of the two evanescent field distributions at different terminal loads. It is shown that the essential principle of wireless energy transfer is the superposition of the two evanescent fields, and the resulting superimposed field is mediated through the terminal load. If the terminal load is either capacitive or inductive, then the superimposed field cannot transfer the energy because its Poynting vector is zero; in contrast, if the load is resistive, energy can then be conveyed from the transmitting coil to the receiving coil. The simulation results for the magnetic field distributions and the time-domain current waveforms agree very well with the results of the theoretical analysis. This work thus provides a comprehensive understanding of the energy transfer mechanism involved in the magnetic resonant coupling system.
Female rats with severe left ventricle volume overload exhibit more cardiac hypertrophy but fewer myocardial transcriptional changes than males
Authors: Beaumont Catherine , Walsh-Wilkinson Élisabeth , Drolet Marie-Claude , Roussel Élise , Arsenault Marie , Couet Jacques 
Published: April 2017

AbstractAortic valve regurgitation (AR) imposes a volume overload (VO) to the left ventricle (LV). Male rats with a pathological heart overload usually progress more quickly towards heart failure than females. We examined whether a sexual dimorphism exists in the myocardial transcriptional adaptations to AR. Adult Wistar male and female rats either underwent a sham operation or were induced with AR and then followed for 26 weeks. Female AR rats gained relatively more LV mass than males (75 vs. 42%). They had a similar increase in LV chamber dimensions compared to males but more wall thickening. On the other hand, fatty acid oxidation (FAO)-related LV enzyme activity was only decreased in AR males. The expression of genes encoding FAO-related enzymes was only reduced in AR males and not in females. A similar situation was observed for the expression of genes involved in mitochondrial biogenesis or function as well as for genes encoding for transcription factors implicated in the control of bioenergetics and mitochondrial function (Errα, Errγ or Pgc1α). Although females develop more LV hypertrophy from severe VO, their myocardial gene expression remains closer to normal. This could provide survival benefits for females with severe VO.
Exploring functions of long noncoding RNAs across multiple cancers through co-expression network
Authors: Li Suqing , Li Bin , Zheng Yuanting , Li Menglong , Shi Leming , Pu Xuemei 
Published: April 2017

AbstractIn contrast to protein-coding genes, long-noncoding RNAs (lncRNAs) are much less well understood, despite increasing evidence indicating a wide range of their biological functions, and possible roles in various cancers. Based on public RNA-seq datasets of four solid cancer types, we here utilize Weighted Correlation Network Analysis (WGCNA) to propose a strategy for exploring the functions of lncRNAs altered in more than two cancer types, which we call onco-lncRNAs. Results indicate that cancer-expressed lncRNAs show high tissue specificity and are weakly expressed, more so than protein-coding genes. Most of the 236 onco-lncRNAs we identified have not been reported to have associations with cancers before. Our analysis exploits co-expression network to reveal that onco-lncRNAs likely play key roles in the multistep development of human cancers, covering a wide range of functions in genome stability maintenance, signaling, cell adhesion and motility, morphogenesis, cell cycle, immune and inflammatory response. These observations contribute to a more comprehensive understanding of cancer-associated lncRNAs, while demonstrating a novel and efficient strategy for subsequent functional studies of lncRNAs.
Split-gated point-contact for electrostatic confinement of transport in MoS2/h-BN hybrid structures
Authors: Sharma Chithra H. , Thalakulam Madhu 
Published: April 2017

AbstractElectrostatically defined nanoscale devices on two-dimensional semiconductor heterostructures are the building blocks of various quantum electrical circuits. Owing to its atomically flat interfaces and the inherent two-dimensional nature, van der Waals heterostructures hold the advantage of large-scale uniformity, flexibility and portability over the conventional bulk semiconductor heterostructures. In this letter we show the operation of a split-gate defined point contact device on a MoS2/h-BN heterostructure, the first step towards realizing electrostatically gated quantum circuits on van der Waals semiconductors. By controlling the voltage on the split-gate we are able to control and confine the electron flow in the device leading to the formation of the point contact. The formation of the point contact in our device is elucidated by the three characteristic regimes observed in the pinch-off curve; transport similar to the conventional FET, electrostatically confined transport and the tunneling dominated transport. We explore the role of the carrier concentration and the drain-source voltages on the pinch-off characteristics. We are able to tune the pinch-off characteristics by varying the back-gate voltage at temperatures ranging from 4 K to 300 K.