bluuebunny/crossref_metadata_2025 huggingface dataset:
The dynamics of the antibiotic resistome in the feces of freshly weaned pigs following therapeutic administration of oxytetracycline
Authors: Ghanbari Mahdi , Klose Viviana , Crispie Fiona , Cotter Paul D.
Published: March 2019

In this study, shotgun metagenomics was employed to monitor the effect of oxytetracycline, administered at a therapeutic dose, on the dynamics of the microbiota and resistome in the feces of weaned pigs. Sixteen weaning pigs were assigned to one of two treatments including standard starter diet for 21 days or antibiotic-supplemented diet (10 g oxytetracycline/100 kg body weight/day) for 7 days, followed by 14 days of standard starter diet. Feces were collected from the pigs on days 0, 8, and 21 for microbiota and resistome profiling. Pigs receiving oxytetracycline exhibited a significantly greater richness (ANOVA, P = 0.034) and diversity (ANOVA, P = 0.048) of antibiotic resistance genes (ARGs) than the control pigs. Antibiotic administration significantly enriched the abundances of 41 ARGs, mainly from the tetracycline, betalactam and multidrug resistance classes. Compositional shifts in the bacterial communities were observed following 7 days of antibiotic adminstration, with the medicated pigs showing an increase in Escherichia (Proteobacteria) and Prevotella (Bacteroidetes) populations compared with the nonmedicated pigs. This might be explained by the potential of these taxa to carry ARGs that may be transferred to other susceptible bacteria in the densely populated gut environment. These findings will help in the optimization of therapeutic schemes involving antibiotic usage in swine production.
A bismuth triiodide monosheet on Bi2Se3(0001)
Authors: Polyakov Andrey , Mohseni Katayoon , Castro German R. , Rubio-Zuazo Juan , Zeugner Alexander , Isaeva Anna , Chen Ying-Jiun , Tusche Christian , Meyerheim Holger L.
Published: March 2019

A stable BiI3 monosheet has been grown for the first time on the (0001) surface of the topological insulator Bi2Se3 as confirmed by scanning tunnelling microscopy, surface X-ray diffraction, and X-ray photoemision spectroscopy. BiI3 is deposited by molecular beam epitaxy from the crystalline BiTeI precursor that undergoes decomposition sublimation. The key fragment of the bulk BiI3 structure, $${{\rm{a}}}_{\infty }^{2}$$

a

∞

2

[I—Bi—I] layer of edge-sharing BiI6 octahedra, is preserved in the ultra-thin film limit, but exhibits large atomic relaxations. The stacking sequence of the trilayers and alternations of the Bi—I distances in the monosheet are the same as in the bulk BiI3 structure. Momentum resolved photoemission spectroscopy indicates a direct band gap of 1.2 eV. The Dirac surface state is completely destroyed and a new flat band appears in the band gap of the BiI3 film that could be interpreted as an interface state.
Synthesis, Characterisation and In Vitro Permeation, Dissolution and Cytotoxic Evaluation of Ruthenium(II)-Liganded Sulpiride and Amino Alcohol
Authors: M’bitsi-Ibouily Gretta C. , Marimuthu Thashree , Kumar Pradeep , Choonara Yahya E. , du Toit Lisa C. , Pradeep Priyamvada , Modi Girish , Pillay Viness
Published: March 2019

Sulpiride (SPR) is a selective antagonist of central dopamine receptors but has limited clinical use due to its poor pharmacokinetics. The aim of this study was to investigate how metal ligation to SPR may improve its solubility, intestinal permeability and prolong its half-life. The synthesis and characterisation of ternary metal complexes [Ru(p -cymene)(L)(SPR)]PF6 (L1 = (R)-(+)-2-amino-3-phenyl-1-propanol, L2 = ethanolamine, L3 = (S)-(+)-2-amino-1-propanol, L4 = 3-amino-1-propanol, L5 = (S)-(+)-2-pyrrolidinemethanol) are described in this work. The stability constant of the [Ru(p -cymene)(SPR)] complex was determined using Job’s method. The obtained value revealed higher stability of the metal complex in the physiological pH than in an acidic environment such as the stomach. The ternary metal complexes were characterised by elemental analysis, Fourier transform infrared spectroscopy (FT-IR), 1H and 13C nuclear magnetic resonance (NMR), differential scanning calorimetry (DSC), thermal analyses, Ultraviolet-Visible (UV-Vis). Solubility studies showed higher aqueous solubility for complexed SPR than the free drug. Dissolution profiles of SPR from the metal complexes exhibited slower dissolution rate of the drug. Permeation studies through the pig’s intestine revealed enhanced membrane permeation of the complexed drug. In vitro methyl thiazolyl tetrazolium (MTT) assay showed no noticeable toxic effects of the ternary metal complexes on Caco-2 cell line.
High-Electrical-Conductivity Multilayer Graphene Formed by Layer Exchange with Controlled Thickness and Interlayer
Authors: Murata Hiromasa , Nakajima Yoshiki , Saitoh Noriyuki , Yoshizawa Noriko , Suemasu Takashi , Toko Kaoru
Published: March 2019

The layer exchange technique enables high-quality multilayer graphene (MLG) on arbitrary substrates, which is a key to combining advanced electronic devices with carbon materials. We synthesize uniform MLG layers of various thicknesses, t, ranging from 5 nm to 200 nm using Ni-induced layer exchange at 800 °C. Raman and transmission electron microscopy studies show the crystal quality of MLG is relatively low for t ≤ 20 nm and dramatically improves for t ≥ 50 nm when we prepare a diffusion controlling Al2O3 interlayer between the C and Ni layers. Hall effect measurements reveal the carrier mobility for t = 50 nm is 550 cm2/Vs, which is the highest Hall mobility in MLG directly formed on an insulator. The electrical conductivity (2700 S/cm) also exceeds a highly oriented pyrolytic graphite synthesized at 3000 °C or higher. Synthesis technology of MLG with a wide range of thicknesses will enable exploration of extensive device applications of carbon materials.
Cargo diffusion shortens single-kinesin runs at low viscous drag
Authors: Wilson John O. , Quint David A. , Gopinathan Ajay , Xu Jing
Published: March 2019

Molecular motors such as kinesin-1 drive active, long-range transport of cargos along microtubules in cells. Thermal diffusion of the cargo can impose a randomly directed, fluctuating mechanical load on the motor carrying the cargo. Recent experiments highlighted a strong asymmetry in the sensitivity of single-kinesin run length to load direction, raising the intriguing possibility that cargo diffusion may non-trivially influence motor run length. To test this possibility, here we employed Monte Carlo-based simulations to evaluate the transport of cargo by a single kinesin. Our simulations included physiologically relevant viscous drag on the cargo and interrogated a large parameter space of cytoplasmic viscosities, cargo sizes, and motor velocities that captures their respective ranges in living cells. We found that cargo diffusion significantly shortens single-kinesin runs. This diffusion-based shortening is countered by viscous drag, leading to an unexpected, non-monotonic variation in run length as viscous drag increases. To our knowledge, this is the first identification of a significant effect of cargo diffusion on motor-based transport. Our study highlights the importance of cargo diffusion and load-detachment kinetics on single-motor functions under physiologically relevant conditions.
Molecular architecture of the Jumonji C family histone demethylase KDM5B
Authors: Dorosz Jerzy , Kristensen Line Hyltoft , Aduri Nanda G. , Mirza Osman , Lousen Rikke , Bucciarelli Saskia , Mehta Ved , Sellés-Baiget Selene , Solbak Sara Marie Øie , Bach Anders , Mesa Pablo , Hernandez Pablo Alcon , Montoya Guillermo , Nguyen Tam T. T. N. , Rand Kasper D. , Boesen Thomas , Gajhede Michael
Published: March 2019

The full length human histone 3 lysine 4 demethylase KDM5B (PLU-1/Jarid1B) has been studied using Hydrogen/Deuterium exchange mass spectrometry, homology modelling, sequence analysis, small angle X-ray scattering and electron microscopy. This first structure on an intact multi-domain Jumonji histone demethylase reveal that the so-called PLU region, in the central region of KDM5B, has a curved α-helical three-dimensional structure, that acts as a rigid linker between the catalytic core and a region comprising four α-helices, a loop comprising the PHD2 domain, two large intrinsically disordered loops and the PHD3 domain in close proximity. The dumbbell shaped and curved KDM5B architecture observed by electron microscopy is complementary to the nucleosome surface and has a striking overall similarity to that of the functionally related KDM1A/CoREST complex. This could suggest that there are similarities between the demethylation mechanisms employed by the two histone 3 lysine 4 demethylases at the molecular level.
PGC-1α overexpression partially rescues impaired oxidative and contractile pathophysiology following volumetric muscle loss injury
Authors: Southern William M. , Nichenko Anna S. , Tehrani Kayvan F. , McGranahan Melissa J. , Krishnan Laxminarayanan , Qualls Anita E. , Jenkins Nathan T. , Mortensen Luke J. , Yin Hang , Yin Amelia , Guldberg Robert E. , Greising Sarah M. , Call Jarrod A.
Published: March 2019

Volumetric muscle loss (VML) injury is characterized by a non-recoverable loss of muscle fibers due to ablative surgery or severe orthopaedic trauma, that results in chronic functional impairments of the soft tissue. Currently, the effects of VML on the oxidative capacity and adaptability of the remaining injured muscle are unclear. A better understanding of this pathophysiology could significantly shape how VML-injured patients and clinicians approach regenerative medicine and rehabilitation following injury. Herein, the data indicated that VML-injured muscle has diminished mitochondrial content and function (i.e., oxidative capacity), loss of mitochondrial network organization, and attenuated oxidative adaptations to exercise. However, forced PGC-1α over-expression rescued the deficits in oxidative capacity and muscle strength. This implicates physiological activation of PGC1-α as a limiting factor in VML-injured muscle’s adaptive capacity to exercise and provides a mechanistic target for regenerative rehabilitation approaches to address the skeletal muscle dysfunction.
Effect of insertion layer on electrode properties in magnetic tunnel junctions with a zero-moment half-metal
Authors: Titova Aleksandra , Fowley Ciarán , Clifford Eugene , Lau Yong-Chang , Borisov Kiril , Betto Davide , Atcheson Gwenael , Hübner René , Xu Chi , Stamenov Plamen , Coey Michael , Rode Karsten , Lindner Jürgen , Fassbender Jürgen , Deac Alina Maria
Published: March 2019

Due to its negligible spontaneous magnetization, high spin polarization and giant perpendicular magnetic anisotropy, Mn2RuxGa (MRG) is an ideal candidate as an oscillating layer in THz spin-transfer-torque nano-oscillators. Here, the effect of ultrathin Al and Ta diffusion barriers between MRG and MgO in perpendicular magnetic tunnel junctions is investigated and compared to devices with a bare MRG/MgO interface. Both the compensation temperature, Tcomp, of the electrode and the tunneling magnetoresistance (TMR) of the device are highly sensitive to the choice and thickness of the insertion layer used. High-resolution transmission electron microscopy, as well as analysis of the TMR, its bias dependence, and the resistance-area product allow us to compare the devices from a structural and electrical point of view. Al insertion leads to the formation of thicker effective barriers and gives the highest TMR, at the cost of a reduced Tcomp. Ta is the superior diffusion barrier which retains Tcomp, however, it also leads to a much lower TMR on account of the short spin diffusion length which reduces the tunneling spin polarization. The study shows that fine engineering of the Mn2RuxGa/barrier interface to improve the TMR amplitude is feasible.
Use of machine learning to identify novel, behaviorally active antagonists of the insect odorant receptor co-receptor (Orco) subunit
Authors: Kepchia Devin , Xu Pingxi , Terryn Raymond , Castro Ana , Schürer Stephan C. , Leal Walter S. , Luetje Charles W.
Published: March 2019

Olfaction is a key component of the multimodal approach used by mosquitoes to target and feed on humans, spreading various diseases. Current repellents have drawbacks, necessitating development of more effective agents. In addition to variable odorant specificity subunits, all insect odorant receptors (ORs) contain a conserved odorant receptor co-receptor (Orco) subunit which is an attractive target for repellent development. Orco directed antagonists allosterically inhibit odorant activation of ORs and we previously showed that an airborne Orco antagonist could inhibit insect olfactory behavior. Here, we identify novel, volatile Orco antagonists. We functionally screened 83 structurally diverse compounds against Orco from Anopheles gambiae. Results were used for training machine learning models to rank probable activity of a library of 1280 odorant molecules. Functional testing of a representative subset of predicted active compounds revealed enrichment for Orco antagonists, many structurally distinct from previously known Orco antagonists. Novel Orco antagonist 2-tert-butyl-6-methylphenol (BMP) inhibited odorant responses in electroantennogram and single sensillum recordings in adult Drosophila melanogaster and inhibited OR-mediated olfactory behavior in D. melanogaster larvae. Structure-activity analysis of BMP analogs identified compounds with improved potency. Our results provide a new approach to the discovery of behaviorally active Orco antagonists for eventual use as insect repellents/confusants.
Skeletal Muscle-specific PGC-1α Overexpression Suppresses Atherosclerosis in Apolipoprotein E-Knockout Mice
Authors: Shimba Yuki , Togawa Hanako , Senoo Nanami , Ikeda Masahiko , Miyoshi Noriyuki , Morita Akihito , Miura Shinji
Published: March 2019

Endurance exercise training prevents atherosclerosis. Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) increases myokine secretion from the skeletal muscle, and these myokines have been shown to affect the function of multiple organs. Since endurance exercise training increases PGC-1α expression in skeletal muscles, we investigated whether skeletal muscle-specific PGC-1α overexpression suppresses atherosclerosis. Apolipoprotein E-knockout (ApoE-KO)/PGC-1α mice, which overexpress PGC-1α in the skeletal muscle of ApoE-KO mice, were sacrificed, and the atherosclerotic plaque area, spontaneous activity, plasma lipid profile, and aortic gene expression were measured. Immunohistochemical analyses were also performed. The atherosclerotic lesions in ApoE-KO/PGC-1α mice were 40% smaller than those in ApoE-KO mice, concomitant with the reduction in vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) mRNA and protein levels in the aorta. Spontaneous activity and plasma lipid profiles were not changed by the overexpression of PGC-1α in the skeletal muscle. In human umbilical vein endothelial cells, Irisin and β-aminoisobutyric acid (BAIBA), PGC-1α-dependent myokines, inhibited the tumor necrosis factor α-induced VCAM-1 gene and protein expression. BAIBA also inhibited TNFα-induced MCP-1 gene expression. These results showed that the skeletal muscle-specific overexpression of PGC-1α suppresses atherosclerosis and that PGC-1α-dependent myokines may be involved in the preventive effects observed.
Quantum Correlation in Squeezed Generalized Amplitude Damping Channels with Memory
Authors: Jeong Youngmin , Shin Hyundong
Published: March 2019

A squeezed generalized amplitude damping (SGAD) channel is a quantum channel that models a general noise process incorporating the effects of bath squeezing, dissipation, and decoherence. In this paper, we analyze the dynamics of quantum entanglement and discord in the SGAD channel with memory. By obtaining a stochastic map defining this noisy quantum channel, we derive the concurrence and discord of Werner-like mixed states sent by successive uses of the channel. It is shown that these quantum correlations can be preserved or even generated depending on the initial channel input states, channel parameters, and the degree of channel memory. In particular, the squeezing effect does not contribute to the dynamics of quantum correlation for singlet-like states under correlated noise.
Discovery of NV-5138, the first selective Brain mTORC1 activator
Authors: Sengupta Shomit , Giaime Emilie , Narayan Sridhar , Hahm Seung , Howell Jessica , O’Neill David , Vlasuk George P. , Saiah Eddine
Published: March 2019

The mechanistic target of rapamycin complex 1 (mTORC1) has been linked to several important chronic medical conditions many of which are associated with advancing age. A variety of inputs including the amino acid leucine are required for full mTORC1 activation. The cytoplasmic proteins Sestrin1 and Sestrin2 specifically bind to the multiprotein complex GATOR2 and communicate leucine sufficiency to the mTORC1 pathway activation complex. Herein, we report NV-5138, a novel orally bioavailable compound that binds to Sestrin2 and activates mTORC1 both in vitro and in vivo. NV-5138 like leucine transiently activates mTORC1 in several peripheral tissues, but in contrast to leucine uniquely activates this complex in the brain due lack of metabolism and utilization in protein synthesis. As such, NV-5138 will permit the exploration in areas of unmet medical need including neuropsychiatric conditions and cognition which have been linked to the activation status of mTORC1.
Frequency specific contribution of intrinsic connectivity networks to the integration in brain networks
Authors: Park Yeong-Hun , Cha Jungho , Bourakova Viktoriya , Lee Jong-Min
Published: March 2019

Brain networks are integrated and segregated into several intrinsic connectivity networks (ICNs). Frequency specificity of ICNs have been studied to show that different ICNs have a unqiue contribution to brain network integration along frequencies. The purpose of this study was to evaluate the contribution of individual ICN to brain network integration along their frequency. We used 14 ICNs and determined 2 frequency bands (LF1, 0.03~0.08 Hz and LF2, 0.009~0.012 Hz) from the hierarchical clustering of 101 frequency bins. We proposed a novel measure, called ICN efficiency, representing the difference between the global efficiencies of the whole brain network with and without the ICN to evaluate the contribution of the ICN to brain network integration. We found that each ICN had a different ICN efficiency at 2 frequency bands. We also found that the distinct subregions of the same ICN had a frequency specific contribution to brain network integration. Futhermore, the integration with other ICNs of the distinct subregions of the same ICN were different at 2 frequency bands. In conclusion, the contribution of each ICN to brain network integration is frequency specific and distinct subregions of the same ICN have functionally distinct roles with other ICNs at 2 frequency bands.
Aggression and courtship differences found in Drosophila melanogaster from two different microclimates at Evolution Canyon, Israel
Authors: Palavicino-Maggio Caroline B. , Trannoy Séverine , Holton Kristina M. , Song Xiaoying , Li Kexin , Nevo Eviatar
Published: March 2019

Aggression and courtship behavior were examined of wild Drosophila melanogaster flies isolated from two contrasting microclimates found at Evolution Canyon in Mt. Carmel, Israel: an African-like dry tropical Slope (AS) and a European-like humid temperate Slope (ES), separated by 250 meters. Studies were carried out to ask whether behavioral differences existed between the two populations obtained from opposite slopes with divergent microclimates in Israel. First, we measured and compared intraslope aggression between same sex fly pairings collected from the same slope. Both male and female flies displayed similar fighting abilities from both slopes. ES males, however, from the humid biome, showed a tendency to lunge more per aggressive encounter, compared with AS males from the dry biome. Next, we tested interslope aggression by pairing flies from opposite slopes. ES males displayed higher numbers of lunges, and won more fights against their AS opponents. We also observed enhanced courtship performances in ES compared to AS males. The fighting and courtship superiority seen in ES males could reinforce fitness and pre-mating reproductive isolation mechanisms that underlie incipient sympatric speciation. This may support an evolutionary advantage of adaptively divergent fruit fly aggression phenotypes from different environments.
Ordinal Preferential Attachment: A Self-Organizing Principle Generating Dense Scale-Free Networks
Authors: Haruna Taichi , Gunji Yukio-Pegio
Published: March 2019

Networks are useful representations for analyzing and modeling real-world complex systems. They are often both scale-free and dense: their degree distribution follows a power-law and their average degree grows over time. So far, it has been argued that producing such networks is difficult without externally imposing a suitable cutoff for the scale-free regime. Here, we propose a new growing network model that produces dense scale-free networks with dynamically generated cutoffs. The link formation rule is based on a weak form of preferential attachment depending only on order relations between the degrees of nodes. By this mechanism, our model yields scale-free networks whose scaling exponents can take arbitrary values greater than 1. In particular, the resulting networks are dense when scaling exponents are 2 or less. We analytically study network properties such as the degree distribution, the degree correlation function, and the local clustering coefficient. All analytical calculations are in good agreement with numerical simulations. These results show that both sparse and dense scale-free networks can emerge through the same self-organizing process.
Additive manufacturing titanium components with isotropic or graded properties by hybrid electron beam melting/hot isostatic pressing powder processing
Authors: Hernández-Nava E. , Mahoney P. , Smith C. J. , Donoghue J. , Todd I. , Tammas-Williams S.
Published: March 2019

A methodology has been demonstrated to consolidate Ti-6Al-4V powder without taking it to the liquid state by novel combination of the electron beam melting additive manufacture and hot isostatic pressing processes. This results in improved static mechanical properties (both strength and yield) in comparison to standard EBM processed material. In addition, the ability to generate microstructurally graded components has been demonstrated by generating a component with a significant change in both microstructure and mechanical properties. This is revealed by the use of electron backscattered diffraction and micro hardness testing to produce maps showing a clear distinction between materials consolidated in different ways. The variation in microstructure and mechanical properties is attributed to the different thermal history experienced by the material at different locations. In particular, it is found that the rapid cooling experienced during EBM leads to a typical fine α lath structure, whereas a more equiaxed α grains generated by diffusion is found in HIP consolidated powder.
Establishment of Novel Murine Model showing Vascular Inflammation-derived Cognitive Dysfunction
Authors: Hashizume Tsuyoshi , Son Bo-Kyung , Taniguchi Sakiko , Ito Koichi , Noda Yoshihiro , Endo Tamao , Nanao-Hamai Michiko , Ogawa Sumito , Akishita Masahiro
Published: March 2019

Inflammation is a critical feature of aging and its related diseases, including cardiovascular diseases. Recent epidemiological studies demonstrated that abdominal aortic aneurysm (AAA), an aging-related vascular pathological condition, is associated with cognitive decline. However, the underlying mechanism, especially the role of vascular inflammation, is largely unknown because of lack of an available animal model. In this study, we examined whether vascular inflammation affects synaptic and cognitive dysfunction, using an AAA mouse model. In young (3 months) and middle-aged (12 months) C57BL/6J mice, AAA was induced by angiotensin II infusion with calcium chloride application. After 4 weeks of induction, aortic diameter was significantly increased and excessive Mac3-positive inflammatory cells infiltrated the destroyed aorta in middle-aged mice. AAA-induced middle-aged mice further exhibited cognitive impairment. Neuronal loss was observed in the CA3 region of the hippocampus. IBA1/MHCII-double-positive microglia activation was also seen in the hippocampus, suggesting that vascular inflammation drives neuroinflammation and subsequent cognitive dysfunction. Furthermore, we found that senescence-accelerated mice prone 8 exhibited robust AAA formation and a marked decrease of cognitive and synaptic function in the hippocampus mediated by inflammation. In conclusion, this novel murine model convincingly suggested the occurrence of vascular inflammation-derived cognitive dysfunction.
Early Evolution of the Mitogen-Activated Protein Kinase Family in the Plant Kingdom
Authors: Kalapos Balázs , Hlavová Monika , Nádai Tímea V. , Galiba Gábor , Bišová Kateřina , Dóczi Róbert
Published: March 2019

Mitogen-activated protein kinase (MAPK) pathways are central cellular signalling mechanisms in all eukaryotes. They are key regulators of the cell cycle and stress responses, yet evolution of MAPK families took markedly different paths in the animal and plant kingdoms. Instead of the characteristic divergence of MAPK types in animals, in plants an expanded network of ERK-like MAPKs has emerged. To gain insight into the early evolution of the plant MAPK family we identified and analysed MAPKs in 13 representative species across green algae, a large and diverse early-diverging lineage within the plant kingdom. Our results reveal that the plant MAPK gene family emerged from three types of progenitor kinases, which are ubiquitously present in algae, implying their formation in an early ancestor. Low number of MAPKs is characteristic across algae, the few losses or duplications are associated with genome complexity rather than habitat ecology, despite the importance of MAPKs in environmental signalling in flowering plants. ERK-type MAPKs are associated with cell cycle regulation in opisthokont models, yet in plants their stress-signalling function is more prevalent. Unicellular microalgae offer an excellent experimental system to study the cell cycle, and MAPK gene expression profiles show CDKB-like peaks around S/M phase in synchronised Chlamydomonas reinhardtii cultures, suggesting their participation in cell cycle regulation, in line with the notion that the ancestral eukaryotic MAPK was a cell cycle regulator ERK-like kinase. Our work also highlights the scarcity of signalling knowledge in microalgae, in spite of their enormous ecological impact and emerging economic importance.
PKD1 Duplicated regions limit clinical Utility of Whole Exome Sequencing for Genetic Diagnosis of Autosomal Dominant Polycystic Kidney Disease
Authors: Ali Hamad , Al-Mulla Fahd , Hussain Naser , Naim Medhat , Asbeutah Akram M. , AlSahow Ali , Abu-Farha Mohamed , Abubaker Jehad , Al Madhoun Ashraf , Ahmad Sajjad , Harris Peter C.
Published: March 2019

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited monogenic renal disease characterised by the accumulation of clusters of fluid-filled cysts in the kidneys and is caused by mutations in PKD1 or PKD2 genes. ADPKD genetic diagnosis is complicated by PKD1 pseudogenes located proximal to the original gene with a high degree of homology. The next generation sequencing (NGS) technology including whole exome sequencing (WES) and whole genome sequencing (WGS), is becoming more affordable and its use in the detection of ADPKD mutations for diagnostic and research purposes more widespread. However, how well does NGS technology compare with the Gold standard (Sanger sequencing) in the detection of ADPKD mutations? Is a question that remains to be answered. We have evaluated the efficacy of WES, WGS and targeted enrichment methodologies in detecting ADPKD mutations in the PKD1 and PKD2 genes in patients who were clinically evaluated by ultrasonography and renal function tests. Our results showed that WES detected PKD1 mutations in ADPKD patients with 50% sensitivity, as the reading depth and sequencing quality were low in the duplicated regions of PKD1 (exons 1–32) compared with those of WGS and target enrichment arrays. Our investigation highlights major limitations of WES in ADPKD genetic diagnosis. Enhancing reading depth, quality and sensitivity of WES in the PKD1 duplicated regions (exons 1–32) is crucial for its potential diagnostic or research applications.
Temperature-Controlled Asymmetric Transmission of Electromagnetic Waves
Authors: Liu Meng , Xu Quan , Chen Xieyu , Plum Eric , Li Hua , Zhang Xueqian , Zhang Caihong , Zou Chongwen , Han Jiaguang , Zhang Weili
Published: March 2019

Chiral materials can exhibit different levels of transmission for opposite propagation directions of the same electromagnetic wave. Here we demonstrate thermal switching of asymmetric transmission of linearly polarized terahertz waves. The effect is observed in a terahertz metamaterial containing 3D-chiral metallic inclusions and achiral vanadium dioxide inclusions. The chiral structure exhibits pronounced asymmetric transmission at room temperature when vanadium dioxide is in its insulator phase. As the metamaterial is heated, the insulator-to-metal phase transition of vanadium dioxide effectively renders the structure achiral and the transmission asymmetry vanishes. We demonstrate the effect numerically and experimentally, describe it analytically and explain the underlying physical mechanism based on simulated surface current distributions. Potential applications include directionally asymmetric active devices as well as intensity and polarization modulators for electromagnetic waves.
Friction on water sliders
Authors: Pucci Giuseppe , Ho Ian , Harris Daniel M.
Published: March 2019

A body in motion tends to stay in motion but is often slowed by friction. Here we investigate the friction experienced by centimeter-sized bodies sliding on water. We show that their motion is dominated by skin friction due to the boundary layer that forms in the fluid beneath the body. We develop a simple model that considers the boundary layer as quasi-steady, and is able to capture the experimental behaviour for a range of body sizes, masses, shapes and fluid viscosities. Furthermore, we demonstrate that friction can be reduced by modification of the body’s shape or bottom topography. Our results are significant for understanding natural and artificial bodies moving at the air-water interface, and can inform the design of aerial-aquatic microrobots for environmental exploration and monitoring.
A Multicenter Study on Early Outcomes of Small-Incision Lenticule Extraction for Myopia
Authors: Kamiya Kazutaka , Takahashi Masahide , Nakamura Tomoaki , Kojima Takashi , Toda Ikuko , Kariya Maro
Published: March 2019

This study was aimed to investigate the early clinical outcomes of small-incision lenticule extraction (SMILE) to correct both myopia and myopic astigmatism at major clinical centers in Japan. This case series consisted of two hundred fifty-two eyes of 130 consecutive patients who underwent SMILE surgery (29.5 ± 6.3 years, mean age ± standard deviation), with spherical equivalents of −4.33 ± 1.61 D. We determined the safety, efficacy, predictability, stability, and adverse events of this procedure. Corrected distance visual acuity significantly improved, from −0.18 ± 0.04 preoperatively to −0.19 ± 0.07 logMAR postoperatively (paired t-test, p < 0.001). Uncorrected distance visual acuity also significantly improved, from 1.05 ± 0.26 preoperatively to −0.15 ± 0.11 logMAR postoperatively (p < 0.001). 88% and 98% of eyes were within ± 0.5 and 1.0 D of the targeted correction, respectively. Changes in manifest spherical equivalent from 1 week postoperatively were 0.02 ± 0.35 D (p = 0.127). No vision-threatening complications were observed in any of the cases. SMILE performed well in the correction of myopic refractive errors, and we experienced no severe complications in this series, indicating its feasibility as a surgical option for the treatment of these eyes.
Vibrio cholerae autoinducer-1 enhances the virulence of enteropathogenic Escherichia coli
Authors: Gorelik Orna , Levy Niva , Shaulov Lihi , Yegodayev Ksenia , Meijler Michael M. , Sal-Man Neta
Published: March 2019

Diarrhoea is the second leading cause of death in children under the age of five. The bacterial species, Vibrio cholerae and enteropathogenic Escherichia coli (EPEC), are among the main pathogens that cause diarrhoeal diseases, which are associated with high mortality rates. These two pathogens have a common infection site—the small intestine. While it is known that both pathogens utilize quorum sensing (QS) to determine their population size, it is not yet clear whether potential bacterial competitors can also use this information. In this study, we examined the ability of EPEC to determine V. cholerae population sizes and to modulate its own virulence mechanisms accordingly. We found that EPEC virulence is enhanced in response to elevated concentrations of cholera autoinducer-1 (CAI-1), even though neither a CAI-1 synthase nor CAI-1 receptors have been reported in E. coli. This CAI-1 sensing and virulence upregulation response may facilitate the ability of EPEC to coordinate successful colonization of a host co-infected with V. cholerae. To the best of our knowledge, this is the first observed example of ‘eavesdropping’ between two bacterial pathogens that is based on interspecies sensing of a QS molecule.
Early life stress delays hippocampal development and diminishes the adult stem cell pool in mice
Authors: Youssef Mary , Atsak Piray , Cardenas Jovani , Kosmidis Stylianos , Leonardo E. David , Dranovsky Alex
Published: March 2019

Early life stress predisposes to mental illness and behavioral dysfunction in adulthood, but the mechanisms underlying these persistent effects are poorly understood. Stress throughout life impairs the structure and function of the hippocampus, a brain system undergoing considerable development in early life. The long-term behavioral consequences of early life stress may therefore be due in part to interference with hippocampal development, in particular with assembly of the dentate gyrus (DG) region of the hippocampus. We investigated how early life stress produces long-term alterations in DG structure by examining DG assembly and the generation of a stable adult stem cell pool in routine housing and after stress induced by the limited bedding/nesting paradigm in mice. We found that early life stress leads to a more immature, proliferative DG than would be expected for the animal’s age immediately after stress exposure, suggesting that early life stress delays DG development. Adult animals exposed to early life stress exhibited a reduction in the number of DG stem cells, but unchanged neurogenesis suggesting a depletion of the stem cell pool with compensation in the birth and survival of adult-born neurons. These results suggest a developmental mechanism by which early life stress can induce long-term changes in hippocampal function by interfering with DG assembly and ultimately diminishing the adult stem cell pool.
Nutrient-based diet modifications impact on the gut microbiome of the Javan slow loris (Nycticebus javanicus)
Authors: Cabana F. , Clayton J. B. , Nekaris K. A. I. , Wirdateti W. , Knights D. , Seedorf H.
Published: March 2019

Environment and diet are key factors which shape the microbiome of organisms. There is also a disparity between captive and wild animals of the same species, presumably because of the change in diet. Being able to reverse the microbiome to the wild type is thus particularly important for the reintroduction efforts of Critically Endangered animals. The Javan slow loris (Nycticebus javanicus) is a suitable model, being kept in the thousands within rescue centres throughout Southeast Asia. With next-generation sequencing, we show how a naturalistic diet impacts the gut microbiome of captive slow lorises (Primates: Nycticebus). A comparison of the microbiome of wild animals with captive animals that had been fed a standard captive or improved diet reveals strong microbiome differences between wild and captive animals; however, diet changes failed to alter the microbiome of captive populations significantly. Bifidobacterium was the most abundant genus in wild animals (46.7%) while Bacteroides (11.6%) and Prevotella (18.9%) were the most abundant in captive animals fed the captive and improved diets, respectively. Correlation analyses of nutrients with microbial taxa suggest important implications in using nutrition to suppress potential pathogens, with soluble fibre and water-soluble carbohydrates both being associated with opposing microbiome profiles. The improved diet significantly increased microbe diversity, which exemplifies the importance of high fibre diets; however, wild individuals had lower diversity, which contradicts recent studies. Detection of methanogens appeared to be dependent on diet and whether the animals were living in captivity or in the wild. This study highlights the potential of nutrition in modulating the microbiome of animals prior to release. Unexpectedly, the results were not as significant as has been suggested in recent studies.
Long-term transmission of entangled photons from a single quantum dot over deployed fiber
Authors: Xiang Zi-Heng , Huwer Jan , Stevenson R. Mark , Skiba-Szymanska Joanna , Ward Martin B. , Farrer Ian , Ritchie David A. , Shields Andrew J.
Published: March 2019

Entangled light sources are considered as core technology for multiple quantum network architectures. Of particular interest are sources that are based on a single quantum system as these offer intrinsic security due to the sub-Poissonian nature of the photon emission process. This is important for applications in quantum communication where multi-pair emission generally compromises performance. A large variety of sources has been developed, but the generated photons remained far from being utilized in established standard fiber networks, mainly due to lack of compatibility with telecommunication wavelengths. In this regard, single semiconductor quantum dots are highly promising photon pair sources as they can be engineered for direct emission at telecom wavelengths. In this work we demonstrate the feasibility of this approach. We report a week-long transmission of polarization-entangled photons from a single InAs/GaAs quantum dot over a metropolitan network fiber. The photons are in the telecommunication O-band, favored for fiber optical communication. We employ a polarization stabilization system overcoming changes of birefringence introduced by 18.23 km of installed fiber. Stable transmission of polarization-encoded entanglement with a high fidelity of 91% is achieved, facilitating the operation of sub-Poissonian quantum light sources over existing fiber networks.
High glucose levels affect retinal patterning during zebrafish embryogenesis
Authors: Singh Amitoj , Castillo Hozana Andrade , Brown Julie , Kaslin Jan , Dwyer Karen M. , Gibert Yann
Published: March 2019

Maternal hyperglycaemia has a profound impact on the developing foetus and increases the risk of developing abnormalities like obesity, impaired glucose tolerance and insulin secretory defects in the post-natal life. Increased levels of glucose in the blood stream due to diabetes causes visual disorders like retinopathy. However, the impact of maternal hyperglycaemia due to pre-existing or gestational diabetes on the developing foetal retina is unknown. The aim of this work was to study the effect of hyperglycaemia on the developing retina using zebrafish as a vertebrate model. Wild-type and transgenic zebrafish embryos were exposed to 0, 4 and 5% D-Glucose in a pulsatile manner to mimic the fluctuations in glycaemia experienced by the developing foetus in pregnant women with diabetes. The zebrafish embryos displayed numerous ocular defects associated with altered retinal cell layer thickness, increased presence of macrophages, and decreased number of Müeller glial and retinal ganglion cells following high-glucose exposure. We have developed a model of gestational hyperglycaemia using the zebrafish embryo to study the effect of hyperglycaemia on the developing embryonic retina. The data suggests that glucose exposure is detrimental to the development of embryonic retina and the legacy of this exposure may extend into adulthood. These data suggest merit in retinal assessment in infants born to mothers with pre-existing and gestational diabetes both in early and adult life.
Whole-Exome Sequencing in the Isolated Populations of Cilento from South Italy
Authors: Nutile T. , Ruggiero D. , Herzig A. F. , Tirozzi A. , Nappo S. , Sorice R. , Marangio F. , Bellenguez C. , Leutenegger A. L. , Ciullo M.
Published: March 2019

The present study describes the genetic architecture of the isolated populations of Cilento, through the analysis of exome sequence data of 245 representative individuals of these populations. By annotating the exome variants and cataloguing them according to their frequency and functional effects, we identified 347,684 variants, 67.4% of which are rare and low frequency variants, and 1% of them (corresponding to 319 variants per person) are classified as high functional impact variants; also, 39,946 (11.5% of the total) are novel variants, for which we determined a significant enrichment for deleterious effects. By comparing the allele frequencies in Cilento with those from the Tuscan population from the 1000 Genomes Project Phase 3, we highlighted an increase in allele frequency in Cilento especially for variants which map to genes involved in extracellular matrix formation and organization. Furthermore, among the variants showing increased frequency we identified several known rare disease-causing variants. By different population genetics analyses, we corroborated the status of the Cilento populations as genetic isolates. Finally, we showed that exome data of Cilento represents a useful local reference panel capable of improving the accuracy of genetic imputation, thus adding power to genetic studies of human traits in these populations.
Raman detection of hidden phonons assisted by atomic point defects in a two-dimensional semimetal
Authors: Yuan Hui , Zhou Xieyu , Cao Yan , Bian Qi , Zhang Zongyuan , Sun Haigen , Li Shaojian , Shao Zhibin , Hu Jin , Zhu Yanglin , Mao Zhiqiang , Ji Wei , Pan Minghu
Published: March 2019

Defects usually have an important role in tailoring various properties of two-dimensional (2D) materials. However, optical detection of defects, especially single-atom point defects, is very challenging in 2D layers. Here, we report our systematic studies on the Raman-activated defect vibrational modes in 2D semimetallic material by combining Raman spectroscopy, density functional theory (DFT) calculation and scanning tunneling microscopy (STM). We observed three common Raman-active vibrational modes located at 95 ($$A_{1g}^2$$

A

1
g

2

), 228 ($$A_{1g}^1$$

A

1
g

1

), and 304 cm−1 ($$B_{1g}^1$$

B

1
g

1

) in ZrSiTe few-layers, consistent with our theoretical calculations. Moreover, a pronounced mode sitting at 131.7 cm−1 was found in the ZrSiTe monolayer. This mode fades out quickly in the bilayer (2L) and eventually disappears in 4L. The high-resolution STM images and DFT calculations suggest this mode to be an intralayer shear mode at the Brillouin zone boundary which is activated by atomic point defects, and STM-based inelastic tunneling spectrum further confirms the existence of such a defect mode. The appearance of such ‘forbidden’ modes in Raman spectra may pave an avenue for the optical characterization of single-atom point defects in metallic 2D layers.
Developing and adopting safe and effective digital biomarkers to improve patient outcomes
Authors: Coravos Andrea , Khozin Sean , Mandl Kenneth D.
Published: March 2019

Biomarkers are physiologic, pathologic, or anatomic characteristics that are objectively measured and evaluated as an indicator of normal biologic processes, pathologic processes, or biological responses to therapeutic interventions. Recent advances in the development of mobile digitally connected technologies have led to the emergence of a new class of biomarkers measured across multiple layers of hardware and software. Quantified in ones and zeros, these “digital” biomarkers can support continuous measurements outside the physical confines of the clinical environment. The modular software–hardware combination of these products has created new opportunities for patient care and biomedical research, enabling remote monitoring and decentralized clinical trial designs. However, a systematic approach to assessing the quality and utility of digital biomarkers to ensure an appropriate balance between their safety and effectiveness is needed. This paper outlines key considerations for the development and evaluation of digital biomarkers, examining their role in clinical research and routine patient care.
Rapid screening of colistin-resistantEscherichia coli,Acinetobacter baumanniiandPseudomonas aeruginosaby the use of Raman spectroscopy and hierarchical cluster analysis
Authors: Lin Zhongquan , Zhao Xiang , Huang Jiaoqi , Liu Wei , Zheng Yuting , Yang Xiang , Zhang Yang , Lamy de la Chapelle Marc , Fu Weiling
Published: March 2019

A fast and reliable detection of colistin resistance inEscherichia coli,Acinetobacter baumanniiandPseudomonas aeruginosa viaRaman spectroscopy.
Magnetic dispersive micro-solid phase extraction with the CuO/ZnO@Fe3O4-CNTs nanocomposite sorbent for the rapid pre-concentration of chlorogenic acid in the medical extract of plants, food, and water samples
Authors: Alipanahpour Dil Ebrahim , Asfaram Arash , Sadeghfar Fardin
Published: March 2019

CuO/ZnO@Fe3O4-CNTs-NC was synthesized and used as a sorbent in a MDMSPE method for the determination of chlorogenic acid in the medical extract of plants, food, and water samples.
Label-free density-based detection of adipocytes of bone marrow origin using magnetic levitation
Authors: Sarigil Oyku , Anil-Inevi Muge , Yilmaz Esra , Mese Gulistan , Tekin H. Cumhur , Ozcivici Engin
Published: March 2019

The first report on application of magnetic levitation technology for detection of adipogenic cells based on single cell density measurement.
Squeezing electrons out of 6s2 lone-pairs in perovskite-type oxides
Authors: Wang Chun-Hai , Kayser Paula , Kennedy Brendan J. , Maynard-Casely Helen E. , Gu Qinfen , Ling Chris D.
Published: March 2019

Unit cell volume collapse in Ba2BiRuO6, Ba2BiIrO6 and Ba2BiOsO6 when Bi(iii) is oxidised to Bi(v) by external applied pressure.
Novel strategy for improving the oxygen permeability of zirconia-based dual-phase membranes
Authors: Kwon Young-il , Park Jong Hyuk , Kang Sin Myung , Nam Gyeong Duk , Lee Jung Won , Kim Jin Ho , Kim Dongyoung , Jeong Sang Mun , Yu Ji Haeng , Joo Jong Hoon
Published: March 2019

This study suggests a breakthrough strategy for greatly improving the oxygen permeability in zirconia/perovskite dual-phase membranes by applying a new coating material that can inhibit secondary phase formation and accelerate the exchange reaction at the membrane surface.
Robust and durable self-healing superhydrophobic polymer-coated MWCNT film for highly efficient emulsion separation
Authors: Ye Hanchen , Chen Dongyun , Li Najun , Xu Qingfeng , Li Hua , He Jinghui , Lu Jianmei
Published: March 2019

The discharge of large amounts of oily wastewater causes serious environmental pollution and is a threat to human health.
Anti-inflammation effects of fucosylated chondroitin sulphate from Acaudina molpadioides by altering gut microbiota in obese mice
Authors: Hu Shiwei , Wang Jinhui , Xu Yangli , Yang Huicheng , Wang Jingfeng , Xue Changhu , Yan Xiaojun , Su Laijinn
Published: March 2019

Fucosylated chondroitin sulfate from Acaudina molpadioides (Am-CHS) can improve chronic inflammation through modulation of gut microbiota via inhibition of LPS/TLR4 signaling and activation of the SCFAs/AMPK pathway.