bluuebunny/crossref_metadata_2025 huggingface dataset:
lncTCF7 is a negative prognostic factor, and knockdown of lncTCF7 inhibits migration, proliferation and tumorigenicity in glioma
Authors: Gao Xiao , Guo Xing , Xue Hao , Qiu Wei , Guo Xiaofan , Zhang Jinsen , Qian Mingyu , Li Tong , Liu Qinglin , Shen Jie , Deng Lin , Li Gang
Published: December 2017

Long noncoding RNAs (lncRNAs) have been shown to play critical roles in cancer. lncTCF7 (gene symbol: WSPAR) has been reported to maintain stemness in hepatocellular carcinoma (HCC) stem cells. However, little is known about the role of lncTCF7 in glioma. The aim of this study was to identify the role of lncTCF7 in the pathogenesis of glioma. We analysed the relationship of lncTCF7 expression with clinicopathological characteristics in glioma patients. Our results showed that lncTCF7 expression was increased in glioma tissues compared with that in normal brain tissues (P < 0.001). Moreover, lncTCF7 was significantly associated with WHO grade (I–II vs. III–IV; P = 0.006) and tumour size (<3 cm vs. T ≥ 3 cm; P = 0.025). Meanwhile, patients with high lncTCF7 expression levels exhibited markedly worse overall survival prognoses (P < 0.01). Loss of function assays revealed that knockdown of lncTCF7 significantly inhibited glioma cell migration, proliferation and tumorigenicity in vitro and in vivo. Furthermore, we found that hypoxia induced lncTCF7 expression in an autocrine manner through IL-6 in glioma. In conclusion, lncTCF7 may play a vital role in glioma progression and serves as a potential prognostic biomarker in glioma patients, providing new targets for glioma therapy.
Enhancing size based size separation through vertical focus microfluidics using secondary flow in a ridged microchannel
Authors: Tasadduq Bushra , Lam Wilbur , Alexeev Alexander , Sarioglu A. Fatih , Sulchek Todd
Published: December 2017

High throughput size based separation and sorting of bioparticles and cells is critical to a variety of biomedical processing steps for medical diagnostics and pharmaceutical purification. Improving microfluidic size-based particle/cell sorting is a challenge to better address the need for generating more homogeneous subpopulations for study and use. We propose a novel advance to microfluidic sorting devices that uses three-dimensional focusing of the sample to optimally position particles to amplify the size-dependent differences in trajectories caused by differential secondary flows. The result is an increase in the purity of small particles by 35- fold and large particles by 8-fold in comparison to unfocused flow. Our simulated and experimental data reveal for the first time that positioning particles in three-dimensional space can be used to better leverage the differential lateral movement of particles with different sizes as they flow in microchannel with transverse secondary flows. The focusing approach may also be useful to improve positioning of particles with inertial channels with multiple equilibrium positions. This technique performs continuous-flow, high throughput size based sorting of millions of particles and cells in a minute without any pre and post-processing. We have also demonstrated improved enrichment and recovery of white blood cells from human blood.
Cell Assembly in Self-foldable Multi-layered Soft Micro-rolls
Authors: Teshima Tetsuhiko F. , Nakashima Hiroshi , Ueno Yuko , Sasaki Satoshi , Henderson Calum S. , Tsukada Shingo
Published: December 2017

Multi-layered thin films with heterogeneous mechanical properties can be spontaneously transformed to realise various three-dimensional (3D) geometries. Here, we describe micro-patterned all-polymer films called micro-rolls that we use for encapsulating, manipulating, and observing adherent cells in vitro. The micro-rolls are formed of twin-layered films consisting of two polymers with different levels of mechanical stiffness; therefore they can be fabricated by using the strain engineering and a self-folding rolling process. By controlling the strain of the films geometrically, we can achieve 3D tubular architectures with controllable diameters. Integration with a batch release of sacrificial hydrogel layers provides a high yield and the biocompatibility of the micro-rolls with any length in the release process without cytotoxicity. Thus, the multiple cells can be wrapped in individual micro-rolls and artificially reconstructed into hollow or fibre-shaped cellular 3D constructs that possess the intrinsic morphologies and functions of living tissues. This system can potentially provide 3D bio-interfaces such as those needed for reconstruction and assembly of functional tissues and implantable tissue grafts.
Activity-Dependent Regulation of Alternative Cleavage and Polyadenylation During Hippocampal Long-Term Potentiation
Authors: Fontes Mariana M. , Guvenek Aysegul , Kawaguchi Riki , Zheng Dinghai , Huang Alden , Ho Victoria M. , Chen Patrick B. , Liu Xiaochuan , O’Dell Thomas J. , Coppola Giovanni , Tian Bin , Martin Kelsey C.
Published: December 2017

Long-lasting forms of synaptic plasticity that underlie learning and memory require new transcription and translation for their persistence. The remarkable polarity and compartmentalization of neurons raises questions about the spatial and temporal regulation of gene expression within neurons. Alternative cleavage and polyadenylation (APA) generates mRNA isoforms with different 3′ untranslated regions (3′UTRs) and/or coding sequences. Changes in the 3′UTR composition of mRNAs can alter gene expression by regulating transcript localization, stability and/or translation, while changes in the coding sequences lead to mRNAs encoding distinct proteins. Using specialized 3′ end deep sequencing methods, we undertook a comprehensive analysis of APA following induction of long-term potentiation (LTP) of mouse hippocampal CA3-CA1 synapses. We identified extensive LTP-induced APA changes, including a general trend of 3′UTR shortening and activation of intronic APA isoforms. Comparison with transcriptome profiling indicated that most APA regulatory events were uncoupled from changes in transcript abundance. We further show that specific APA regulatory events can impact expression of two molecules with known functions during LTP, including 3′UTR APA of Notch1 and intronic APA of Creb1. Together, our results reveal that activity-dependent APA provides an important layer of gene regulation during learning and memory.
Discriminating single-bacterial shape using low-aspect-ratio pores
Authors: Tsutsui Makusu , Yoshida Takeshi , Yokota Kazumichi , Yasaki Hirotoshi , Yasui Takao , Arima Akihide , Tonomura Wataru , Nagashima Kazuki , Yanagida Takeshi , Kaji Noritada , Taniguchi Masateru , Washio Takashi , Baba Yoshinobu , Kawai Tomoji
Published: December 2017

Conventional concepts of resistive pulse analysis is to discriminate particles in liquid by the difference in their size through comparing the amount of ionic current blockage. In sharp contrast, we herein report a proof-of-concept demonstration of the shape sensing capability of solid-state pore sensors by leveraging the synergy between nanopore technology and machine learning. We found ionic current spikes of similar patterns for two bacteria reflecting the closely resembled morphology and size in an ultra-low thickness-to-diameter aspect-ratio pore. We examined the feasibility of a machine learning strategy to pattern-analyse the sub-nanoampere corrugations in each ionic current waveform and identify characteristic electrical signatures signifying nanoscopic differences in the microbial shape, thereby demonstrating discrimination of single-bacterial cells with accuracy up to 90%. This data-analytics-driven microporescopy capability opens new applications of resistive pulse analyses for screening viruses and bacteria by their unique morphologies at a single-particle level.
Modeling and optimization of thermal conductivity and viscosity of MnFe2O4 nanofluid under magnetic field using an ANN
Authors: Amani Mohammad , Amani Pouria , Kasaeian Alibakhsh , Mahian Omid , Pop Ioan , Wongwises Somchai
Published: December 2017

This research investigates the applicability of an ANN and genetic algorithms for modeling and multiobjective optimization of the thermal conductivity and viscosity of water-based spinel-type MnFe2O4 nanofluid. Levenberg-Marquardt, quasi-Newton, and resilient backpropagation methods are employed to train the ANN. The support vector machine (SVM) method is also presented for comparative purposes. Experimental results demonstrate the efficacy of the developed ANN with the LM-BR training algorithm and the 3-10-10-2 structure for the prediction of the thermophysical properties of nanofluids in terms of the significantly superior accuracy compared to developing the correlation and employing SVM regression. Moreover, the genetic algorithm is implemented to determine the optimal conditions, i.e., maximum thermal conductivity and minimum nanofluid viscosity, based on the developed ANN.
The Human Blood-Nerve Barrier Transcriptome
Authors: Palladino Steven P. , Helton E. Scott , Jain Preti , Dong Chaoling , Crowley Michael R. , Crossman David K. , Ubogu Eroboghene E.
Published: December 2017

The blood-nerve barrier (BNB), formed by tight junction-forming microvessels within peripheral nerve endoneurium, exists to regulate its internal microenvironment essential for effective axonal signal transduction. Relatively little is known about the unique human BNB molecular composition. Such knowledge is crucial to comprehend the relationships between the systemic circulation and peripheral nerves in health, adaptations to intrinsic or extrinsic perturbations and alterations that may result in disease. We performed RNA-sequencing on cultured early- and late-passage adult primary human endoneurial endothelial cells and laser-capture microdissected endoneurial microvessels from four cryopreserved normal adult human sural nerves referenced to the Genome Reference Consortium Human Reference 37 genome browser, using predefined criteria guided by known transcript or protein expression in vitro and in situ. We identified 12881 common transcripts associated by 125 independent biological networks, defined as the normal adult BNB transcriptome, including a comprehensive array of transporters and specialized intercellular junctional complex components. These identified transcripts and their interacting networks provide insights into peripheral nerve microvascular morphogenesis, restrictive barrier formation, influx and efflux transporters with relevance to understanding peripheral nerve homeostasis and pharmacology, including targeted drug delivery and the mediators of leukocyte trafficking in peripheral nerves during normal immunosurveillance.
Tear proteome analysis in ocular surface diseases using label-free LC-MS/MS and multiplexed-microarray biomarker validation
Authors: Soria Javier , Acera Arantxa , Merayo-LLoves Jesús , Durán Juan A. , González Nerea , Rodriguez Sandra , Bistolas Nikitas , Schumacher Soeren , Bier Frank F. , Peter Harald , Stöcklein Walter , Suárez Tatiana
Published: December 2017

We analyzed the tear film proteome of patients with dry eye (DE), meibomian gland dysfunction (MGD), and normal volunteers (CT). Tear samples were collected from 70 individuals. Of these, 37 samples were analyzed using spectral-counting-based LC-MS/MS label-free quantitation, and 33 samples were evaluated in the validation of candidate biomarkers employing customized antibody microarray assays. Comparative analysis of tear protein profiles revealed differences in the expression levels of 26 proteins, including protein S100A6, annexin A1, cystatin-S, thioredoxin, phospholipase A2, antileukoproteinase, and lactoperoxidase. Antibody microarray validation of CST4, S100A6, and MMP9 confirmed the accuracy of previously reported ELISA assays, with an area under ROC curve (AUC) of 87.5%. Clinical endpoint analysis showed a good correlation between biomarker concentrations and clinical parameters. In conclusion, different sets of proteins differentiate between the groups. Apolipoprotein D, S100A6, S100A8, and ceruloplasmin discriminate best between the DE and CT groups. The differences between antileukoproteinase, phospholipase A2, and lactoperoxidase levels allow the distinction between MGD and DE, and the changes in the levels of annexin A1, clusterin, and alpha-1-acid glycoprotein 1, between MGD and CT groups. The functional network analysis revealed the main biological processes that should be examined to identify new candidate biomarkers and therapeutic targets.
cfDNA correlates with endothelial damage after cardiac surgery with prolonged cardiopulmonary bypass and amplifies NETosis in an intracellular TLR9-independent manner
Authors: Paunel-Görgülü Adnana , Wacker Max , El Aita Mouhamed , Hassan Shoreshfan , Schlachtenberger Georg , Deppe Antje , Choi Yeong-Hoon , Kuhn Elmar , Mehler Thorsten O. , Wahlers Thorsten
Published: December 2017

Cardiopulmonary bypass (CPB) provokes inflammation culminating in organ dysfunction and increased mortality. Recently, neutrophil extracellular traps (NETs) have been found to be involved in a variety of cardiovascular diseases promoting tissue and organ injury. Here, we aimed to elaborate the proinflammatory potential of circulating cell-free (cf)DNA in patients undergoing cardiac surgery with CPB. Plasma was collected pre- and postoperatively as well as at d1, d3, d5 and d8 after surgery. At d1, we found circulating cfDNA levels to be significantly increased in patients with prolonged CPB duration (>100 min) when compared to those with shorter CPB times (CPB < 100 min). Increased CPB duration yielded in higher levels of circulating mitochondrial (mt)DNA, soluble thrombomodulin (sCD141) and ICAM-1, reflecting endothelial damage. Positive correlation between cfDNA and sCD141 was demonstrated at all time points. Plasma and cfDNA from patients with CPB > 100 min induced NETs release by neutrophils from healthy donors which was not suppressed by inhibitors of intracellular toll-like receptor (TLR)9. DNA binding to neutrophils’ surface (s)TLR9 has been evidenced. Altogether, we demonstrate that elevated plasma cfDNA might be useful to assess CPB-mediated detrimental effects, including endothelial damage, in cardiac surgical patients with prolonged CPB duration. cfDNA-triggered NETosis is independent of classical TLR9 signaling.
High-Capacity Free-Space Optical Communications Between a Ground Transmitter and a Ground Receiver via a UAV Using Multiplexing of Multiple Orbital-Angular-Momentum Beams
Authors: Li Long , Zhang Runzhou , Zhao Zhe , Xie Guodong , Liao Peicheng , Pang Kai , Song Haoqian , Liu Cong , Ren Yongxiong , Labroille Guillaume , Jian Pu , Starodubov Dmitry , Lynn Brittany , Bock Robert , Tur Moshe , Willner Alan E.
Published: December 2017

We explore the use of orbital-angular-momentum (OAM)-multiplexing to increase the capacity of free-space data transmission to moving platforms, with an added potential benefit of decreasing the probability of data intercept. Specifically, we experimentally demonstrate and characterize the performance of an OAM-multiplexed, free-space optical (FSO) communications link between a ground transmitter and a ground receiver via a moving unmanned-aerial-vehicle (UAV). We achieve a total capacity of 80 Gbit/s up to 100-m-roundtrip link by multiplexing 2 OAM beams, each carrying a 40-Gbit/s quadrature-phase-shift-keying (QPSK) signal. Moreover, we investigate for static, hovering, and moving conditions the effects of channel impairments, including: misalignments, propeller-induced airflows, power loss, intermodal crosstalk, and system bit error rate (BER). We find the following: (a) when the UAV hovers in the air, the power on the desired mode fluctuates by 2.1 dB, while the crosstalk to the other mode is −19 dB below the power on the desired mode; and (b) when the UAV moves in the air, the power fluctuation on the desired mode increases to 4.3 dB and the crosstalk to the other mode increases to −10 dB. Furthermore, the channel crosstalk decreases with an increase in OAM mode spacing.
The shallow structure of Solfatara Volcano, Italy, revealed by dense, wide-aperture seismic profiling
Authors: Bruno Pier Paolo G. , Maraio Stefano , Festa Gaetano
Published: December 2017

Two active-source, high-resolution seismic profiles were acquired in the Solfatara tuff cone in May and November 2014, with dense, wide-aperture arrays. Common Receiver Surface processing was crucial in improving signal-to-noise ratio and reflector continuity. These surveys provide, for the first time, high-resolution seismic images of the Solfatara crater, depicting a ~400 m deep asymmetrical crater filled by volcanoclastic sediments and rocks and carved within an overall non-reflective pre-eruptive basement showing features consistent with the emplacement of shallow intrusive bodies. Seismic reflection data were interpreted using the trace complex attributes and clearly display several steep and segmented collapse faults, generally having normal kinematics and dipping toward the crater centre. Fault/fracture planes are imaged as sudden amplitude drops that generate narrow low-similarity and high-dip attributes. Uprising fluids degassed by a magmatic source are the most probable cause of the small-scale amplitude reduction. Seismic data also support the interpretation of the shallow structure of the Solfatara crater as a maar. Our results provides a solid framework to constrain the near-surface geological interpretation of such a complex area, which improves our understanding of the temporal changes of the structure in relation with other geophysical and geochemical measurements.
Impact of treatment on resting cerebral blood flow and metabolism in obsessive compulsive disorder: a meta-analysis
Authors: van der Straten A. L. , Denys D. , van Wingen G. A.
Published: December 2017

Neurobiological models of obsessive-compulsive disorder (OCD) posit that its clinical symptoms such as repetitive thoughts and behaviors are related to hyperactivity in the cortico–striato–thalamo–cortical (CSTC) circuit. Small scale neuroimaging studies have shown that treatment of OCD is associated with reduced activity across different brain structures within this circuitry. We performed the first meta-analysis of positron emission tomography (PET) and single photon emission computed tomography (SPECT) studies that investigated cerebral blood flow or glucose metabolism in patients with OCD before and after pharmacological or psychological treatment. We calculated standardized mean differences for the regions-of-interest most often reported. The meta-analysis revealed small reductions in activity in the caudate nucleus and orbitofrontal cortex after treatment with a serotonin reuptake inhibitor or cognitive behavioral therapy. Small reductions were also observed in the thalamus when one SPECT study with a large opposite effect was excluded from the analysis. Meta-regression analyses for the caudate nucleus showed no significant effect of the type of treatment, decrease in symptom severity, mean duration until the follow-up scan, or year of publication. These results show that pharmacological and psychological treatments reduce resting CSTC circuit activity, and provide further support for the CSTC circuit model in OCD.
The AP-1 transcription factor JunB is required for Th17 cell differentiation
Authors: Yamazaki Soh , Tanaka Yoshihiko , Araki Hiromitsu , Kohda Akira , Sanematsu Fumiyuki , Arasaki Tomoko , Duan Xuefeng , Miura Fumihito , Katagiri Takaharu , Shindo Ryodai , Nakano Hiroyasu , Ito Takashi , Fukui Yoshinori , Endo Shogo , Sumimoto Hideki
Published: December 2017

Interleukin (IL)-17-producing T helper (Th17) cells are crucial for host defense against extracellular microbes and pathogenesis of autoimmune diseases. Here we show that the AP-1 transcription factor JunB is required for Th17 cell development.Junb-deficient CD4+T cells are able to developin vitrointo various helper T subsets except Th17. The RNA-seq transcriptome analysis reveals that JunB is crucial for the Th17-specific gene expression program.Junb-deficient mice are completely resistant to experimental autoimmune encephalomyelitis, a Th17-mediated inflammatory disease, and naive T helper cells from such mice fail to differentiate into Th17 cells. JunB appears to activate Th17 signature genes by forming a heterodimer with BATF, another AP-1 factor essential for Th17 differentiation. The mechanism whereby JunB controls Th17 cell development likely involves activation of the genes for the Th17 lineage-specifying orphan receptors RORγt and RORα and reduced expression of Foxp3, a transcription factor known to antagonize RORγt function.
Soil biota in vineyards are more influenced by plants and soil quality than by tillage intensity or the surrounding landscape
Authors: Buchholz Jacob , Querner Pascal , Paredes Daniel , Bauer Thomas , Strauss Peter , Guernion Muriel , Scimia Jennifer , Cluzeau Daniel , Burel Françoise , Kratschmer Sophie , Winter Silvia , Potthoff Martin , Zaller Johann G.
Published: December 2017

Tillage is known for its adverse effects on soil biota, at least in arable agroecosystems. However, in vineyards effects might differ as tillage is often performed during dry periods or only in every other inter-row allowing species to re-colonise disturbed areas. We examined the response of earthworms (lumbricids), springtails (collembola) and litter decomposition to periodically mechanically disturbed (PMD) and permanently green covered (PGC) vineyard inter-rows and assessed whether site effects are altered by the surrounding landscape. In commercial vineyards in Austria we sampled earthworms by handsorting, springtails by soil coring and pitfall trapping and installed litter decomposition bags. Earthworm species diversity increased with plant biomass under PMD but not under PGC; earthworm density was unaffected by tillage but increased with plant biomass mainly at high soil quality (soil fertility index). Springtail species diversity was unaffected by tillage; springtail densities (mainly larger species) were reduced under PGC. Litter decomposition was little affected by investigated parameters. Landscape heterogeneity affected the functional diversity of surface springtails, but did not influence soil-dwelling springtails, earthworms or litter decomposition. We conclude that effects on soil biota of periodical tillage in vineyards need not necessarily be detrimental and will be modified by plant biomass and soil quality.
Electron nematic effect induced by magnetic field in antiferroquadrupole phase of CeB
6
Authors: Demishev S. V. , Krasnorussky V. N. , Bogach A. V. , Voronov V. V. , Shitsevalova N. Yu. , Filipov V. B. , Glushkov V. V. , Sluchanko N. E.
Published: December 2017

Spatial anisotropy generated spontaneously in the translationally invariant metallic phase, i.e. electron nematic effect, addresses a great challenge for both experimentalists and theoreticians. An interesting option for the realization of the electron nematic phase is provided by the system with orbital ordering, as long as both orbitally ordered states and electron nematic phases possess broken spatial symmetry. Here we report the detailed study of the angular dependences of the magnetoresistance in the orbitally ordered antiferroquadrupole (AFQ) phase of CeB6. Our data allowed revealing the electron nematic effect, which develops when magnetic field exceeds a critical value of 0.3–0.5T. As a result, new transition inside the AFQ phase corresponding to the change of the symmetry of magnetic scattering on spin fluctuations in CeB6 is discovered.
Genomic diversity and macroecology of the crop wild relatives of domesticated pea
Authors: Smýkal Petr , Hradilová Iveta , Trněný Oldřich , Brus Jan , Rathore Abhishek , Bariotakis Michael , Das Roma Rani , Bhattacharyya Debjyoti , Richards Christopher , Coyne Clarice J. , Pirintsos Stergios
Published: December 2017

There is growing interest in the conservation and utilization of crop wild relatives (CWR) in international food security policy and research. Legumes play an important role in human health, sustainable food production, global food security, and the resilience of current agricultural systems. Pea belongs to the ancient set of cultivated plants of the Near East domestication center and remains an important crop today. Based on genome-wide analysis, P. fulvum was identified as a well-supported species, while the diversity of wild P. sativum subsp. elatius was structured into 5 partly geographically positioned clusters. We explored the spatial and environmental patterns of two progenitor species of domesticated pea in the Mediterranean Basin and in the Fertile Crescent in relation to the past and current climate. This study revealed that isolation by distance does not explain the genetic structure of P. sativum subsp. elatius in its westward expansion from its center of origin. The genetic diversity of wild pea may be driven by Miocene-Pliocene events, while the phylogenetic diversity centers may reflect Pleisto-Holocene climatic changes. These findings help set research and discussion priorities and provide geographical and ecological information for germplasm-collecting missions, as well as for the preservation of extant diversity in ex-situ collections.
A different vision of dyslexia: Local precedence on global perception
Authors: Franceschini Sandro , Bertoni Sara , Gianesini Tiziana , Gori Simone , Facoetti Andrea
Published: December 2017

Individuals perceive the wor(l)d hierarchically. Firsty, the global visual scene is processed by the right hemisphere, and later, the local features are perceived by the left hemisphere. Based on this hierarchical analysis, humans evolved unique communication ability: reading. However, for about 10% of people reading acquisition is extremely difficult, they are affected by a heritable neurodevelopmental disorder called dyslexia. Differences in perceiving the wor(l)d might be one of the causes of reading disabilities. Here we show multiple causal links between the global before local perception and learning to read. Five behavioral experiments in 353 children reveal that: (i) a local before global perception characterizes three independent groups of unselected children with dyslexia; (ii) two global before local perception trainings improve reading skills in children with dyslexia; and stringently (iii) pre-reading local before global perception longitudinally predicts future poor readers. Challenging the uni-causal and left-lateralized phonological explanation of dyslexia, our results demonstrate that learning to read depends also on an efficient right neural network for the global analysis of the visual scene. These results provide new insights in learning strategies and pave the way for early identification and possible prevention programs.
Non-malignant epithelial cells preferentially proliferate from nasopharyngeal carcinoma biopsy cultured under conditionally reprogrammed conditions
Authors: Yu Fenggang , Lu Yanan , Tao Lin , Jiang Yan-Yi , Lin De-Chen , Wang Lingzhi , Petersson Fredrik , Yoshiyama Hironori , Koeffler Phillip H. , Goh Boon-Cher , Loh Kwok Seng
Published: December 2017

Nasopharyngeal carcinoma (NPC) is an invasive cancer with particularly high incidence in Southern China and Southeast Asia. The study of NPC is greatly hampered by the lack of reliable cell lines due to the loss of EBV genome and HeLa cell contamination. Conditional reprogramming (CR) cell culture technique has been reported for rapid and efficient establishment of patient‐derived normal and tumor cell cultures. The purpose of this study was to assess this method to culture NPC patient‐derived primary tumor cells. Using CR protocol, we demonstrated that epithelial cells could be efficiently cultured from normal (70%) and cancerous nasopharyngeal (46%) biopsies. However, by comparing with original tumors in terms of mutation and methylation profiles, epithelial cells derived from cancerous biopsy represented non‐malignant cells. Further, they exhibited stem‐like characteristics based on their cell surface proteins and could differentiate into pseudostratified epithelium in an air–liquid interface culture system. We conclude that CR method is a highly selective and useful method for growing non‐malignant nasopharyngeal epithelial cells.
Macroscopic phase separation of superconductivity and ferromagnetism in Sr0.5Ce0.5FBiS2−x
Se
x
revealed by μSR
Authors: Nikitin A. M. , Grinenko V. , Sarkar R. , Orain J.-C. , Salis M. V. , Henke J. , Huang Y. K. , Klauss H.-H. , Amato A. , Visser A. de
Published: December 2017

The compound Sr0.5Ce0.5FBiS2 belongs to the intensively studied family of layered BiS2 superconductors. It attracts special attention because superconductivity at T
sc
 = 2.8 K was found to coexist with local-moment ferromagnetic order with a Curie temperature T
C
 = 7.5 K. Recently it was reported that upon replacing S by Se T
C
drops and ferromagnetism becomes of an itinerant nature. At the same time T
sc
increases and it was argued superconductivity coexists with itinerant ferromagnetism. Here we report a muon spin rotation and relaxation study (μSR) conducted to investigate the coexistence of superconductivity and ferromagnetic order in Sr0.5Ce0.5FBiS2−x
Se
x
with x = 0.5 and 1.0. By inspecting the muon asymmetry function we find that both phases do not coexist on the microscopic scale, but occupy different sample volumes. For x = 0.5 and x = 1.0 we find a ferromagnetic volume fraction of ~8 % and ~30 % at T = 0.25 K, well below T
C
 = 3.4 K and T
C
 = 3.3 K, respectively. For x = 1.0 (T
sc
 = 2.9 K) the superconducting phase occupies most (~64 %) of the remaining sample volume, as shown by transverse field experiments that probe the Gaussian damping due to the vortex lattice. We conclude ferromagnetism and superconductivity are macroscopically phase separated.
An Exhaustive Search Algorithm to Aid NMR-Based Structure Determination of Rotationally Symmetric Transmembrane Oligomers
Authors: Yang Jing , Piai Alessandro , Shen Hong-Bin , Chou James J.
Published: December 2017

Nuclear magnetic resonance (NMR) has been an important source of structural restraints for solving structures of oligomeric transmembrane domains (TMDs) of cell surface receptors and viral membrane proteins. In NMR studies, oligomers are assembled using inter-protomer distance restraints. But, for oligomers that are higher than dimer, these distance restraints all have two-fold directional ambiguity, and resolving such ambiguity often requires time-consuming trial-and-error calculations using restrained molecular dynamics (MD) with simulated annealing (SA). We report an Exhaustive Search algorithm for Symmetric Oligomer (ExSSO), which can perform near-complete search of the symmetric conformational space in a very short time. In this approach, the predetermined protomer model is subject to full angular and spatial search within the symmetry space. This approach, which can be applied to any rotationally symmetric oligomers, was validated using the structures of the Fas death receptor, the HIV-1 gp41 fusion protein, the influenza proton channel, and the MCU pore. The algorithm is able to generate approximate oligomer solutions quickly as initial inputs for further refinement using the MD/SA method.
Mother-to-newborn transmission of mycobacterial L-forms and Vδ2 T-cell response in placentobiome of BCG-vaccinated pregnant women
Authors: Dimova T. , Terzieva A. , Djerov L. , Dimitrova V. , Nikolov A. , Grozdanov P. , Markova N.
Published: December 2017

The ability of bacteria to exist as a population of self-replicating forms with defective or entirely missing cell wall (L-forms) is an adaptive mechanism for their survival and reproduction under unfavorable conditions. Bacterial mother-to-fetus transfer is a universal phenomenon in the animal kingdom. However, data about vertical transfer of L bacterial forms are extremely scarce. Bacille Calmette-Guérin is an attenuated strain of M. bovis and the only licensed vaccine used for tuberculosis prevention. We already have shown that filterable L-forms of BCG exist freely in the vaccine and are able to reproduce and to form colonies. The present study was focused on the placental microbiome in the context of mother’s BCG vaccination. Here we report an isolation of filterable mycobacterial L-form cultures from gestational tissues and blood of healthy newborns delivered by healthy BCG-vaccinated mothers after normal pregnancy. Of note, vertically transmitted mycobacterial L-forms as a part of placentobiome of the pregnant women didn’t influence the number of resident pathogen-reactive Vδ2 cells. Placenta colonization with mycobacterial L-forms occurs by maternal blood-to-decidua transfer very early in gestation. Together, these data showed that BCG L-forms have the capacity to pass trans-placental barrier and that maternal BCG vaccination affects the placentobiome.
Facile Fabrication of Porous Conductive Thermoplastic Polyurethane Nanocomposite Films via Solution Casting
Authors: Wu Tongfei , Chen Biqiong
Published: December 2017

Porous conductive polymers are one of important materials, featuring lightweight, large specific surface area and high porosity. Non-solvent induced phase separation is widely employed to prepare porous polymer sheet materials. Through utilizing water vapor in ambient environment as the non-solvent, a facile approach was developed to produce porous conductive polymer nanocomposites using the conventional solution-casting method. Without using any non-solvent liquids, porous carbon nanofiber/thermoplastic polyurethane (CNF/TPU) nanocomposites were prepared directly by solution casting of their dimethylformamide (DMF) solutions under ambient conditions. The strength of the CNF framework played a key role in preventing the collapse of pores during DMF evaporation. The dependence of porous structures on CNF loading was studied by scanning electron microscopy and porosity measurement. The influence of CNF loading on the mechanical properties, electrical conductivity and piezoresistive behavior was explored.
Nod2 is required for the early innate immune clearance of Acinetobacter baumannii from the lungs
Authors: Kale Sandeep D. , Dikshit Neha , Kumar Pankaj , Balamuralidhar Vanniarajan , Khameneh Hanif Javanmard , Bin Abdul Malik Najib , Koh Tse Hsien , Tan Gladys Gek Yen , Tan Thuan Tong , Mortellaro Alessandra , Sukumaran Bindu
Published: December 2017

Acinetobacter baumannii (A. baumannii) is a significant cause of severe nosocomial pneumonia in immunocompromised individuals world-wide. With limited treatment options available, a better understanding of host immnity to A. baumannii infection is critical to devise alternative control strategies. Our previous study has identified that intracellular Nod1/Nod2 signaling pathway is required for the immune control of A. baumannii in airway epithelial cells in vitro. In the current study, using Nod2−/− mice and an in vivo sublethal model of pulmonary infection, we show that Nod2 contributes to the early lung defense against A. baumannii infection through reactive oxygen species (ROS)/reactive nitrogen species (RNS) production as Nod2−/− mice showed significantly reduced production of ROS/RNS in the lungs following A. baumannii infection. Consistent with the higher bacterial load, A. baumannii-induced neutrophil recruitment, cytokine/chemokine response and lung pathology was also exacerbated in Nod2−/− mice at early time points post-infection. Finally, we show that administration of Nod2 ligand muramyl dipeptide (MDP) prior to infection protected the wild- type mice from A. baumannii pulmonary challenge. Collectively, Nod2 is an important player in the early lung immunity against A. baumannii and modulating Nod2 pathway could be considered as a viable therapeutic strategy to control A. baumannii pulmonary infection.
Repeatability of corneal elevation maps in keratoconus patients using the tomography matching method
Authors: Zheng YaRu , Huang LiFang , Zhao YiPing , Wang JunJie , Zheng XiaoBo , Huang Wei , Geraghty Brendan , Wang QinMei , Chen ShiHao , Bao FangJun , Elsheikh Ahmed
Published: December 2017

To assess repeatability of corneal tomography in successive measurements by Pentacam in keratoconus (KC) and normal eyes based on the Iterative Closest Point (ICP) algorithm. The study involved 143 keratoconic and 143 matched normal eyes. ICP algorithm was used to estimate six single and combined misalignment (CM) parameters, the root mean square (RMS) of the difference in elevation data pre (PreICP-RMS) and post (PosICP-RMS) tomography matching. Corneal keratometry, expressed in the form of M, J0 and J45 (power vector analysis parameters), was used to evaluate the effect of misalignment on corneal curvature measurements. The PreICP-RMS and PosICP-RMS were statistically higher (P < 0.01) in KC than normal eyes. CM increased significantly (p = 0.00), more in KC (16.76 ± 20.88 μm) than in normal eyes (5.43 ± 4.08 μm). PreICP-RMS, PosICP-RMS and CM were correlated with keratoconus grade (p < 0.05). Corneal astigmatism J0 was different (p = 0.01) for the second tomography measurements with misalignment consideration (−1.11 ± 2.35 D) or not (−1.18 ± 2.35 D), while M and J45 kept similar. KC corneas consistently show higher misalignments between successive tomography measurements and lower repeatability compared with healthy eyes. The influence of misalignment is evidently clearer in the estimation of astigmatism than spherical curvature. These higher errors appear correlated with KC progression.
In silico modelling to differentiate the contribution of sugar frequency versus total amount in driving biofilm dysbiosis in dental caries
Authors: Head David , A. Devine Deirdre , Marsh P. D.
Published: December 2017

Dental caries is the most prevalent infection globally and a substantial economic burden in developed countries. Dietary sugars are the main risk factor, and drive increased proportions of acid-producing and acid-tolerating (aciduric) bacterial species within dental biofilms. Recent longitudinal studies have suggested that caries is most strongly correlated with total sugar intake, contrasting with the prevailing view that intake frequency is the primary determinant. To explore this possibility, we employed a computational model for supragingival plaque to systematically sample combinations of sugar frequency and total amount, allowing their independent contributions on the ratio of aciduric (i.e. cariogenic) to non-aciduric bacteria to be unambiguously determined. Sugar frequency was found to be irrelevant for either very high or very low daily total amounts as the simulated biofilm was predicted to be always or never cariogenic, respectively. Frequency was a determining factor for intermediate total amounts of sugar, including the estimated average human consumption. An increased risk of caries (i.e. high prevalence of aciduric/non-aciduric species) was predicted for high intake frequencies. Thus, both total amount and frequency of sugar intake may combine to influence plaque cariogenicity. These findings could be employed to support public guidance for dietary change, leading to improved oral healthcare.
Rebound of Cotton leaf curl Multan virus and its exclusive detection in cotton leaf curl disease outbreak, Punjab (India), 2015
Authors: Datta Sibnarayan , Budhauliya Raghvendra , Das Bidisha , Gopalakrishnan Reji , Sharma Sonika , Chatterjee Soumya , Vanlalhmuaka  , Raju P. Srinivas , Veer Vijay
Published: December 2017

Cotton leaf curl disease (CLCuD) outbreaks caused by CLCuD associated begomoviruses (CABs) significantly constrain cotton production in India and Pakistan. In comparison to the CABs circulating in Pakistan, molecular epidemiology, evolution and recombination patterns of CABs circulating in India are less studied. In this work, we characterized CAB complex sequences obtained from the most recent outbreak (Punjab, India, 2015), and rigorously analyzed them with reference to GenBank sequences, submitted from India, Pakistan and other neighbouring countries, using contemporary bioinformatics approaches. In this manuscript, we illustrate the detection of a recombinant, phylogenetically distinct clade of Cotton leaf curl Multan virus (CLCuMuV), suggesting rebound of CLCuMuV in this region. Interestingly, we could not detect Cotton leaf curl Kokhran virus-Burewala strain (CLCuKoV-Bu), which was prevalent in this region, until now. Our study thus indicates substitution of the ‘virulent resistance breaking’ CLCuKoV-Bu by the re-emerging CLCuMuV recombinants. Our findings corroborate with that of a very recent study from Pakistan and we here discuss epidemiological links between the CAB complexes reported in these two studies. Taken together, these observations signify a shifting epidemiology of CABs, and seem to correlate with the recent prediction of the ‘third epidemic’ of CLCuD in the Indian subcontinent.
The Human DNA glycosylases NEIL1 and NEIL3 Excise Psoralen-Induced DNA-DNA Cross-Links in a Four-Stranded DNA Structure
Authors: Martin Peter R. , Couvé Sophie , Zutterling Caroline , Albelazi Mustafa S. , Groisman Regina , Matkarimov Bakhyt T. , Parsons Jason L. , Elder Rhoderick H. , Saparbaev Murat K.
Published: December 2017

Interstrand cross-links (ICLs) are highly cytotoxic DNA lesions that block DNA replication and transcription by preventing strand separation. Previously, we demonstrated that the bacterial and human DNA glycosylases Nei and NEIL1 excise unhooked psoralen-derived ICLs in three-stranded DNA via hydrolysis of the glycosidic bond between the crosslinked base and deoxyribose sugar. Furthermore, NEIL3 from Xenopus laevis has been shown to cleave psoralen- and abasic site-induced ICLs in Xenopus egg extracts. Here we report that human NEIL3 cleaves psoralen-induced DNA-DNA cross-links in three-stranded and four-stranded DNA substrates to generate unhooked DNA fragments containing either an abasic site or a psoralen-thymine monoadduct. Furthermore, while Nei and NEIL1 also cleave a psoralen-induced four-stranded DNA substrate to generate two unhooked DNA duplexes with a nick, NEIL3 targets both DNA strands in the ICL without generating single-strand breaks. The DNA substrate specificities of these Nei-like enzymes imply the occurrence of long uninterrupted three- and four-stranded crosslinked DNA-DNA structures that may originate in vivo from DNA replication fork bypass of an ICL. In conclusion, the Nei-like DNA glycosylases unhook psoralen-derived ICLs in various DNA structures via a genuine repair mechanism in which complex DNA lesions can be removed without generation of highly toxic double-strand breaks.
Probing the requirement for CD38 in retinoic acid-induced HL-60 cell differentiation with a small molecule dimerizer and genetic knockout
Authors: MacDonald Robert J. , Shrimp Jonathan H. , Jiang Hong , Zhang Lu , Lin Hening , Yen Andrew
Published: December 2017

CD38 is an ectoenzyme and receptor with key physiological roles. It metabolizes NAD+to adenosine diphosphate ribose (ADPR) and cyclic ADPR, regulating several processes including calcium signalling. CD38 is both a positive and negative prognostic indicator in leukaemia. In all-transretinoic acid (RA)-induced differentiation of acute promyelocytic leukaemia and HL-60 cells, CD38 is one of the earliest and most prominently upregulated proteins known. CD38 overexpression enhances differentiation, while morpholino- and siRNA-induced knockdown diminishes it. CD38, via Src family kinases and adapters, interacts with a MAPK signalling axis that propels differentiation. Motivated by evidence suggesting the importance of CD38, we sought to determine whether it functions via dimerization. We created a linker based on the suicide substrate arabinosyl-2′-fluoro-2′-deoxy NAD+(F-araNAD+), dimeric F-araNAD+, to induce homodimerization. CD38 homodimerization did not affect RA-induced differentiation. Probing the importance of CD38 further, we created HL-60 cell lines with CRISPR/Cas9-mediated CD38 truncations. Deletion of its enzymatic domain did not affect differentiation. Apart from increased RA-induced CD11b expression, ablation of all but the first six amino acids of CD38 affected neither RA-induced differentiation nor associated signalling. Although we cannot discount the importance of this peptide, our study indicates that CD38 is not necessary for RA-induced differentiation.
Enclaves of genetic diversity resisted Inca impacts on population history
Authors: Barbieri Chiara , Sandoval José R. , Valqui Jairo , Shimelman Aviva , Ziemendorff Stefan , Schröder Roland , Geppert Maria , Roewer Lutz , Gray Russell , Stoneking Mark , Fujita Ricardo , Heggarty Paul
Published: December 2017

The Inca Empire is claimed to have driven massive population movements in western South America, and to have spread Quechua, the most widely-spoken language family of the indigenous Americas. A test-case is the Chachapoyas region of northern Peru, reported as a focal point of Inca population displacements. Chachapoyas also spans the environmental, cultural and demographic divides between Amazonia and the Andes, and stands along the lowest-altitude corridor from the rainforest to the Pacific coast. Following a sampling strategy informed by linguistic data, we collected 119 samples, analysed for full mtDNA genomes and Y-chromosome STRs. We report a high indigenous component, which stands apart from the network of intense genetic exchange in the core central zone of Andean civilization, and is also distinct from neighbouring populations. This unique genetic profile challenges the routine assumption of large-scale population relocations by the Incas. Furthermore, speakers of Chachapoyas Quechua are found to share no particular genetic similarity or gene-flow with Quechua speakers elsewhere, suggesting that here the language spread primarily by cultural diffusion, not migration. Our results demonstrate how population genetics, when fully guided by the archaeological, historical and linguistic records, can inform multiple disciplines within anthropology.
High flux water purification using aluminium hydroxide hydrate gels
Authors: Malekizadeh Ali , Schenk Peer M.
Published: December 2017

Filtration of aqueous liquids has wide implications, for example for provision of clean drinking water. Nevertheless, many people still lack access to safe water and suffer from preventable water-borne microbial diseases. This study reports a new ultrafiltration-range separation technology using a gelatinous layer of aluminium hydroxide polyhydrate as a secondary membrane on a retaining fabric that enables simple and cost-effective production of filtered water. Properties include at least 4-fold higher flux rates than currently available membranes, pressure-resistance, impenetrability to filtered particles, easy cleaning by backwashing and simple, cost-effective replacement by gel injection. Depending on the substrate, filtration is achieved through a packed bed of 1–2 nm hydrate gel globules, partly by mechanical straining with a size exclusion of approx. 10 nm and partly by physical adsorption. As a result, filtration of water (e.g. turbid river water) contaminated with colloids and microorganisms, including viruses, yields clear water that is free of measurable particles or detectable microorganisms. However, small water-soluble molecules (salts, sugars, proteins) remain in the filtrate. The findings demonstrate the potential for wide applicability of hydrate gels in high-flux and low-cost water purification devices.