bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptomic signatures of NK cells suggest impaired responsiveness in HIV-1 infection and increased activity post-vaccination
Authors: Costanzo Margaret C. , Kim Dohoon , Creegan Matthew , Lal Kerri G. , Ake Julie A. , Currier Jeffrey R. , Streeck Hendrik , Robb Merlin L. , Michael Nelson L. , Bolton Diane L. , Steers Nicholas J. , Eller Michael A.
Published: April 2018

Natural killer (NK) cells limit viral replication by direct recognition of infected cells, antibody-dependent cellular cytotoxicity (ADCC), and releasing cytokines. Although growing evidence supports NK cell antiviral immunity in HIV-1 infection, further knowledge of their response is necessary. Here we show that NK cells responding to models of direct cell recognition, ADCC, and cytokine activation have unique transcriptional fingerprints. Compared with healthy volunteers, individuals with chronic HIV-1 infection have higher expression of genes commonly associated with activation, and lower expression of genes associated with direct cell recognition and cytokine stimulation in their NK cells. By contrast, NK cell transcriptional profiles of individuals receiving a modified vaccinia Ankara (MVA) vectored HIV-1 vaccine show upregulation of genes associated with direct cell recognition. These findings demonstrate that targeted transcriptional profiling provides a sensitive assessment of NK cell activity, which helps understand how NK cells respond to viral infections and vaccination.
Conformational switching within dynamic oligomers underpins toxic gain-of-function by diabetes-associated amyloid
Authors: Birol Melissa , Kumar Sunil , Rhoades Elizabeth , Miranker Andrew D.
Published: April 2018

Peptide mediated gain-of-toxic function is central to pathology in Alzheimer’s, Parkinson’s and diabetes. In each system, self-assembly into oligomers is observed and can also result in poration of artificial membranes. Structural requirements for poration and the relationship of structure to cytotoxicity is unaddressed. Here we focus on islet amyloid polypeptide (IAPP) mediated loss-of-insulin secreting cells in patients with diabetes. Newly developed methods enable structure-function enquiry to focus on intracellular oligomers composed of hundreds of IAPP. The key insights are that porating oligomers are internally dynamic, grow in discrete steps and are not canonical amyloid. Moreover, two classes of poration occur; an IAPP-specific ligand establishes that only one is cytotoxic. Toxic rescue occurs by stabilising non-toxic poration without displacing IAPP from mitochondria. These insights illuminate cytotoxic mechanism in diabetes and also provide a generalisable approach for enquiry applicable to other partially ordered protein assemblies.
Zeb1-Hdac2-eNOS circuitry identifies early cardiovascular precursors in naive mouse embryonic stem cells
Authors: Cencioni Chiara , Spallotta Francesco , Savoia Matteo , Kuenne Carsten , Guenther Stefan , Re Agnese , Wingert Susanne , Rehage Maike , Sürün Duran , Siragusa Mauro , Smith Jacob G. , Schnütgen Frank , von Melchner Harald , Rieger Michael A. , Martelli Fabio , Riccio Antonella , Fleming Ingrid , Braun Thomas , Zeiher Andreas M. , Farsetti Antonella , Gaetano Carlo
Published: April 2018

Nitric oxide (NO) synthesis is a late event during differentiation of mouse embryonic stem cells (mESC) and occurs after release from serum and leukemia inhibitory factor (LIF). Here we show that after release from pluripotency, a subpopulation of mESC, kept in the naive state by 2i/LIF, expresses endothelial nitric oxide synthase (eNOS) and endogenously synthesizes NO. This eNOS/NO-positive subpopulation (ESNO+) expresses mesendodermal markers and is more efficient in the generation of cardiovascular precursors than eNOS/NO-negative cells. Mechanistically, production of endogenous NO triggers rapid Hdac2 S-nitrosylation, which reduces association of Hdac2 with the transcriptional repression factor Zeb1, allowing mesendodermal gene expression. In conclusion, our results suggest that the interaction between Zeb1, Hdac2, and eNOS is required for early mesendodermal differentiation of naive mESC.
Synthesis of AgN5 and its extended 3D energetic framework
Authors: Sun Chengguo , Zhang Chong , Jiang Chao , Yang Chen , Du Yang , Zhao Yue , Hu Bingcheng , Zheng Zhansheng , Christe Karl O.
Published: April 2018

The pentazolate anion, as a polynitrogen species, holds great promise as a high-energy density material for explosive or propulsion applications. Designing pentazole complexes that contain minimal non-energetic components is desirable in order to increase the material’s energy density. Here, we report a solvent-free pentazolate complex, AgN5, and a 3D energetic-framework, [Ag(NH3)2]+[Ag3(N5)4]ˉ, constructed from silver and cyclo-N5ˉ. The complexes are stable up to 90 °C and only Ag and N2 are observed as the final decomposition products. Efforts to isolate pure AgN5 were unsuccessful due to partial photolytical and/or thermal-decomposition to AgN3. Convincing evidence for the formation of AgN5 as the original reaction product is presented. The isolation of a cyclo-N5ˉ complex, devoid of stabilizing molecules and ions, such as H2O, H3O+, and NH4+, constitutes a major advance in pentazole chemistry.
Two-component anomalous Hall effect in a magnetically doped topological insulator
Authors: Liu Nan , Teng Jing , Li Yongqing
Published: April 2018

The anomalous Hall (AH) effect measurement has emerged as a powerful tool to gain deep insights into magnetic materials, such as ferromagnetic metals, magnetic semiconductors, and magnetic topological insulators (TIs). In Mn-doped Bi2Se3, however, the AH effect has never been reported despite a lot of previous studies. Here we report the observation of AH effect in (Bi,Mn)2Se3 thin films and show that the sign of AH resistances changes from positive to negative as the Mn concentration is increased. The positive and negative AH resistances are found to coexist in a crossover regime. Such a two-component AH effect and the sign reversal can also be obtained by electrical gating of lightly doped samples. Our results provide an important basis for understanding the puzzling interplay between the surface states, the bulk states, and various magnetic doping effects, as well as competing magnetic orders in magnetically doped TIs.
The world’s largest High Arctic lake responds rapidly to climate warming
Authors: Lehnherr Igor , St. Louis Vincent L. , Sharp Martin , Gardner Alex S. , Smol John P. , Schiff Sherry L. , Muir Derek C. G. , Mortimer Colleen A. , Michelutti Neil , Tarnocai Charles , St. Pierre Kyra A. , Emmerton Craig A. , Wiklund Johan A. , Köck Günter , Lamoureux Scott F. , Talbot Charles H.
Published: April 2018

Using a whole-watershed approach and a combination of historical, contemporary, modeled and paleolimnological datasets, we show that the High Arctic’s largest lake by volume (Lake Hazen) has succumbed to climate warming with only a ~1 °C relative increase in summer air temperatures. This warming deepened the soil active layer and triggered large mass losses from the watershed’s glaciers, resulting in a ~10 times increase in delivery of glacial meltwaters, sediment, organic carbon and legacy contaminants to Lake Hazen, a >70% decrease in lake water residence time, and near certainty of summer ice-free conditions. Concomitantly, the community assemblage of diatom primary producers in the lake shifted dramatically with declining ice cover, from shoreline benthic to open-water planktonic species, and the physiological condition of the only fish species in the lake, Arctic Char, declined significantly. Collectively, these changes place Lake Hazen in a biogeochemical, limnological and ecological regime unprecedented within the past ~300 years.
Biosynthesis of fragin is controlled by a novel quorum sensing signal
Authors: Jenul Christian , Sieber Simon , Daeppen Christophe , Mathew Anugraha , Lardi Martina , Pessi Gabriella , Hoepfner Dominic , Neuburger Markus , Linden Anthony , Gademann Karl , Eberl Leo
Published: April 2018

Members of the diazeniumdiolate class of natural compounds show potential for drug development because of their antifungal, antibacterial, antiviral, and antitumor activities. Yet, their biosynthesis has remained elusive to date. Here, we identify a gene cluster directing the biosynthesis of the diazeniumdiolate compound fragin in Burkholderia cenocepacia H111. We provide evidence that fragin is a metallophore and that metal chelation is the molecular basis of its antifungal activity. A subset of the fragin biosynthetic genes is involved in the synthesis of a previously undescribed cell-to-cell signal molecule, valdiazen. RNA-Seq analyses reveal that valdiazen controls fragin biosynthesis and affects the expression of more than 100 genes. Homologs of the valdiazen biosynthesis genes are found in various bacteria, suggesting that valdiazen-like compounds may constitute a new class of signal molecules. We use structural information, in silico prediction of enzymatic functions and biochemical data to propose a biosynthesis route for fragin and valdiazen.
Towards an arthritis flare-responsive drug delivery system
Authors: Joshi Nitin , Yan Jing , Levy Seth , Bhagchandani Sachin , Slaughter Kai V. , Sherman Nicholas E. , Amirault Julian , Wang Yufeng , Riegel Logan , He Xueyin , Rui Tan Shi , Valic Michael , Vemula Praveen K. , Miranda Oscar R. , Levy Oren , Gravallese Ellen M. , Aliprantis Antonios O. , Ermann Joerg , Karp Jeffrey M.
Published: April 2018

Local delivery of therapeutics for the treatment of inflammatory arthritis (IA) is limited by short intra-articular half-lives. Since IA severity often fluctuates over time, a local drug delivery method that titrates drug release to arthritis activity would represent an attractive paradigm in IA therapy. Here we report the development of a hydrogel platform that exhibits disassembly and drug release controlled by the concentration of enzymes expressed during arthritis flares. In vitro, hydrogel loaded with triamcinolone acetonide (TA) releases drug on-demand upon exposure to enzymes or synovial fluid from patients with rheumatoid arthritis. In arthritic mice, hydrogel loaded with a fluorescent dye demonstrates flare-dependent disassembly measured as loss of fluorescence. Moreover, a single dose of TA-loaded hydrogel but not the equivalent dose of locally injected free TA reduces arthritis activity in the injected paw. Together, our data suggest flare-responsive hydrogel as a promising next-generation drug delivery approach for the treatment of IA.
Infused ice can multiply IceCube’s sensitivity
Authors: Bartos Imre , Marka Zsuzsa , Marka Szabolcs
Published: April 2018

The IceCube Neutrino Observatory is the world’s largest neutrino detector with a cubic-kilometer instrumented volume at the South Pole. It is preparing for a major upgrade that will significantly increase its sensitivity. A promising technological innovation investigated for this upgrade is wavelength shifting optics. Augmenting sensors with such optics could increase the photo-collection area of IceCube’s digital optical modules, and shift the incoming photons’ wavelength to where these modules are the most sensitive. Here we investigate the use of IceCube’s drill holes as wavelength shifting optics. We calculate the sensitivity enhancement due to increasing the ice’s refractive index in the holes, and infusing wavelength-shifting substrate into the ice. We find that, with adequate wavelength-shifter infusion, every ~0.05 increase in the ice’s refractive index will increase IceCube’s photon sensitivity by 100%, opening the possibility for the substantial, cost-effective expansion of IceCube’s reach.
Extraordinary pseudocapacitive energy storage triggered by phase transformation in hierarchical vanadium oxides
Authors: Liu Bo-Tian , Shi Xiang-Mei , Lang Xing-You , Gu Lin , Wen Zi , Zhao Ming , Jiang Qing
Published: April 2018

Pseudocapacitance holds great promise for improving energy densities of electrochemical supercapacitors, but state-of-the-art pseudocapacitive materials show capacitances far below their theoretical values and deliver much lower levels of electrical power than carbon-based materials due to poor cation accessibility and/or long-range electron transferability. Here we show that in situ corundum-to-rutile phase transformation in electron-correlated vanadium sesquioxide can yield nonstoichiometric rutile vanadium dioxide layers that are composed of highly sodium ion accessible oxygen-deficiency quasi-hexagonal tunnels sandwiched between conductive rutile slabs. This unique structure serves to boost redox and intercalation kinetics for extraordinary pseudocapacitive energy storage in hierarchical isomeric vanadium oxides, leading to a high specific capacitance of ~1856 F g–1 (almost sixfold that of the pristine vanadium sesquioxide and dioxide) and a bipolar charge/discharge capability at ultrafast rates in aqueous electrolyte. Symmetric wide voltage window pseudocapacitors of vanadium oxides deliver a power density of ~280 W cm–3 together with an exceptionally high volumetric energy density of ~110 mWh cm–3 as well as long-term cycling stability.
Dual-comb spectroscopy of laser-induced plasmas
Authors: Bergevin Jenna , Wu Tsung-Han , Yeak Jeremy , Brumfield Brian E. , Harilal Sivanandan S. , Phillips Mark C. , Jones R. Jason
Published: April 2018

Dual-comb spectroscopy has become a powerful spectroscopic technique in applications that rely on its broad spectral coverage combined with high frequency resolution capabilities. Experiments to date have primarily focused on detection and analysis of multiple gas species under semi-static conditions, with applications ranging from environmental monitoring of greenhouse gases to high-resolution molecular spectroscopy. Here, we utilize dual-comb spectroscopy to demonstrate broadband, high-resolution, and time-resolved measurements in a laser-induced plasma. As a demonstration, we simultaneously detect trace amounts of Rb and K in solid samples with a single laser ablation shot, with transitions separated by over 6 THz (13 nm) and spectral resolution sufficient to resolve isotopic and ground state hyperfine splittings of the Rb D2 line. This new spectroscopic approach offers the broad spectral coverage found in the powerful techniques of laser-induced breakdown spectroscopy (LIBS) while providing the high-resolution and accuracy of cw laser-based spectroscopies.
Burned forests impact water supplies
Authors: Hallema Dennis W. , Sun Ge , Caldwell Peter V. , Norman Steven P. , Cohen Erika C. , Liu Yongqiang , Bladon Kevin D. , McNulty Steven G.
Published: April 2018

Wildland fire impacts on surface freshwater resources have not previously been measured, nor factored into regional water management strategies. But, large wildland fires are increasing and raise concerns about fire impacts on potable water. Here we synthesize long-term records of wildland fire, climate, and river flow for 168 locations across the United States. We show that annual river flow changed in 32 locations, where more than 19% of the basin area was burned. Wildland fires enhanced annual river flow in the western regions with a warm temperate or humid continental climate. Wildland fires increased annual river flow most in the semi-arid Lower Colorado region, in spite of frequent droughts in this region. In contrast, prescribed burns in the subtropical Southeast did not significantly alter river flow. These extremely variable outcomes offer new insights into the potential role of wildfire and prescribed fire in regional water resource management, under a changing climate.
Rolling up transition metal dichalcogenide nanoscrolls via one drop of ethanol
Authors: Cui Xueping , Kong Zhizhi , Gao Enlai , Huang Dazhen , Hao Yang , Shen Hongguang , Di Chong-an , Xu Zhiping , Zheng Jian , Zhu Daoben
Published: April 2018

Two-dimensional transition metal dichalcogenides (TMDs) have attracted lots of interest because of their potential for electronic and optoelectronic applications. Atomically thin TMD flakes were believed capable to scroll into nanoscrolls (NSs) with distinct properties. However, limited by mechanical strength and chemical stability, production of high-quality TMD NSs remains challenging. Here, we scroll chemical vapor deposition-grown monolayer TMD flakes into high-quality NSs in situ in 5 s with a nearly 100% yield by only one droplet of ethanol solution. An obvious photoluminescence is demonstrated in NSs and the self-encapsulated structure makes NSs more insensitive to external factors in optical and electrical properties. Furthermore, based on the internal open topology, NSs hybridized with a variety of functional materials have been fabricated, which is expected to confer TMD NSs with additional properties and functions attractive for potential application.
Endocycle-related tubular cell hypertrophy and progenitor proliferation recover renal function after acute kidney injury
Authors: Lazzeri Elena , Angelotti Maria Lucia , Peired Anna , Conte Carolina , Marschner Julian A. , Maggi Laura , Mazzinghi Benedetta , Lombardi Duccio , Melica Maria Elena , Nardi Sara , Ronconi Elisa , Sisti Alessandro , Antonelli Giulia , Becherucci Francesca , De Chiara Letizia , Guevara Ricardo Romero , Burger Alexa , Schaefer Beat , Annunziato Francesco , Anders Hans-Joachim , Lasagni Laura , Romagnani Paola
Published: April 2018

Acute kidney injury (AKI) is considered largely reversible based on the capacity of surviving tubular cells to dedifferentiate and replace lost cells via cell division. Here we show by tracking individual tubular cells in conditional Pax8/Confetti mice that kidney function is  recovered after AKI despite substantial tubular cell loss. Cell cycle and ploidy analysis upon AKI in conditional Pax8/FUCCI2aR mice and human biopsies identify endocycle-mediated hypertrophy of tubular cells. By contrast, a small subset of Pax2+ tubular progenitors enriches via higher stress resistance and clonal expansion and regenerates necrotic tubule segments, a process that can be enhanced by suitable drugs. Thus,  renal functional recovery upon AKI involves remnant tubular cell hypertrophy via endocycle and limited progenitor-driven regeneration that can be pharmacologically enhanced.
Small molecules promote CRISPR-Cpf1-mediated genome editing in human pluripotent stem cells
Authors: Ma Xiaojie , Chen Xi , Jin Yan , Ge Wenyan , Wang Weiyun , Kong Linghao , Ji Junfang , Guo Xing , Huang Jun , Feng Xin-Hua , Fu Junfen , Zhu Saiyong
Published: April 2018

Human pluripotent stem cells (hPSCs) have potential applications in biological studies and regenerative medicine. However, precise genome editing in hPSCs remains time-consuming and labor-intensive. Here we demonstrate that the recently identified CRISPR-Cpf1 can be used to efficiently generate knockout and knockin hPSC lines. The unique properties of CRISPR-Cpf1, including shorter crRNA length and low off-target activity, are very attractive for many applications. In particular, we develop an unbiased drug-selection-based platform feasible for high-throughput screening in hPSCs and this screening system enables us to identify small molecules VE-822 and AZD-7762 that can promote CRISPR-Cpf1-mediated precise genome editing. Significantly, the combination of CRISPR-Cpf1 and small molecules provides a simple and efficient strategy for precise genome engineering.
Systematic design and experimental demonstration of bianisotropic metasurfaces for scattering-free manipulation of acoustic wavefronts
Authors: Li Junfei , Shen Chen , Díaz-Rubio Ana , Tretyakov Sergei A. , Cummer Steven A.
Published: April 2018

Recent advances in gradient metasurfaces have shown that by locally controlling the bianisotropic response of the cells one can ensure full control of refraction, that is, arbitrarily redirect the waves without scattering into unwanted directions. In this work, we propose and experimentally verify the use of an acoustic cell architecture that provides enough degrees of freedom to fully control the bianisotropic response and minimizes the losses. The versatility of the approach is shown through the design of three refractive metasurfaces capable of redirecting a normally incident plane wave to 60°, 70°, and 80° on transmission. The efficiency of the bianisotropic designs is over 90%, much higher than the corresponding generalized Snell’s law based designs (81%, 58%, and 35%). The proposed strategy opens a new way of designing practical and highly efficient bianisotropic metasurfaces for different functionalities, enabling nearly ideal control over the energy flow through thin metasurfaces.
Structural mechanism for nucleotide-driven remodeling of the AAA-ATPase unfoldase in the activated human 26S proteasome
Authors: Zhu Yanan , Wang Wei Li , Yu Daqi , Ouyang Qi , Lu Ying , Mao Youdong
Published: April 2018

The proteasome is a sophisticated ATP-dependent molecular machine responsible for protein degradation in all known eukaryotic cells. It remains elusive how conformational changes of the AAA-ATPase unfoldase in the regulatory particle (RP) control the gating of the substrate–translocation channel leading to the proteolytic chamber of the core particle (CP). Here we report three alternative states of the ATP-γ-S-bound human proteasome, in which the CP gates are asymmetrically open, visualized by cryo-EM at near-atomic resolutions. At least four nucleotides are bound to the AAA-ATPase ring in these open-gate states. Variation in nucleotide binding gives rise to an axial movement of the pore loops narrowing the substrate-translation channel, which exhibit remarkable structural transitions between the spiral-staircase and saddle-shaped-circle topologies. Gate opening in the CP is thus regulated by nucleotide-driven conformational changes of the AAA-ATPase unfoldase. These findings demonstrate an elegant mechanism of allosteric coordination among sub-machines within the human proteasome holoenzyme.
Land-use change interacts with climate to determine elevational species redistribution
Authors: Guo Fengyi , Lenoir Jonathan , Bonebrake Timothy C.
Published: April 2018

Climate change is driving global species redistribution with profound social and economic impacts. However, species movement is largely constrained by habitat availability and connectivity, of which the interaction effects with climate change remain largely unknown. Here we examine published data on 1464 elevational range shifts from 43 study sites to assess the confounding effect of land-use change on climate-driven species redistribution. We show that baseline forest cover and recent forest cover change are critical predictors in determining the magnitude of elevational range shifts. Forest loss positively interacts with baseline temperature conditions, such that forest loss in warmer regions tends to accelerate species’ upslope movement. Consequently, not only climate but also habitat loss stressors and, importantly, their synergistic effects matter in forecasting species elevational redistribution, especially in the tropics where both stressors will increase the risk of net lowland biotic attrition.
Crab spiders impact floral-signal evolution indirectly through removal of florivores
Authors: Knauer Anina C. , Bakhtiari Moe , Schiestl Florian P.
Published: April 2018

The puzzling diversity of flowers is primarily shaped by selection and evolutionary change caused by the plant’s interaction with animals. The contribution of individual animal species to net selection, however, may vary depending on the network of interacting organisms. Here we document that in the buckler mustard, Biscutella laevigata, the crab spider Thomisus onustus reduces bee visits to flowers but also benefits plants by feeding on florivores. Uninfested plants experience a trade-off between pollinator and spider attraction as both bees and crab spiders are attracted by the floral volatile β-ocimene. This trade-off is reduced by the induced emission of β-ocimene after florivore infestation, which is stronger in plant populations where crab spiders are present than where they are absent, suggesting that plants are locally adapted to the presence of crab spiders. Our study demonstrates the context-dependence of selection and shows how crab spiders impact on floral evolution.
Contraction of basal filopodia controls periodic feather branching via Notch and FGF signaling
Authors: Cheng Dongyang , Yan Xiaoli , Qiu Guofu , Zhang Juan , Wang Hanwei , Feng Tingting , Tian Yarong , Xu Haiping , Wang Meiqing , He Wanzhong , Wu Ping , Widelitz Randall B , Chuong Cheng-Ming , Yue Zhicao
Published: April 2018

Branching morphogenesis is a general mechanism that increases the surface area of an organ. In chicken feathers, the flat epithelial sheath at the base of the follicle is transformed into periodic branches. How exactly the keratinocytes are organized into this pattern remains unclear. Here we show that in the feather follicle, the pre-branch basal keratinocytes have extensive filopodia, which contract and smooth out after branching. Manipulating the filopodia via small GTPases RhoA/Cdc42 also regulates branch formation. These basal filopodia help interpret the proximal-distal FGF gradient in the follicle. Furthermore, the topological arrangement of cell adhesion via E-Cadherin re-distribution controls the branching process. Periodic activation of Notch signaling drives the differential cell adhesion and contraction of basal filopodia, which occurs only below an FGF signaling threshold. Our results suggest a coordinated adjustment of cell shape and adhesion orchestrates feather branching, which is regulated by Notch and FGF signaling.
A high-strength silicide phase in a stainless steel alloy designed for wear-resistant applications
Authors: Bowden D. , Krysiak Y. , Palatinus L. , Tsivoulas D. , Plana-Ruiz S. , Sarakinou E. , Kolb U. , Stewart D. , Preuss M.
Published: April 2018

Hardfacing alloys provide strong, wear-resistant and corrosion-resistant coatings for extreme environments such as those within nuclear reactors. Here, we report an ultra-high-strength Fe–Cr–Ni silicide phase, named π-ferrosilicide, within a hardfacing Fe-based alloy. Electron diffraction tomography has allowed the determination of the atomic structure of this phase. Nanohardness testing indicates that the π-ferrosilicide phase is up to 2.5 times harder than the surrounding austenite and ferrite phases. The compressive strength of the π-ferrosilicide phase is exceptionally high and does not yield despite loading in excess of 1.6 GPa. Such a high-strength silicide phase could not only provide a new type of strong, wear-resistant and corrosion-resistant Fe-based coating, replacing more costly and hazardous Co-based alloys for nuclear applications, but also lead to the development of a new class of high-performance silicide-strengthened stainless steels, no longer reliant on carbon for strengthening.
Improved phase field model of dislocation intersections
Authors: Zheng Songlin , Zheng Dongchang , Ni Yong , He Linghui
Published: April 2018

Revealing the long-range elastic interaction and short-range core reaction between intersecting dislocations is crucial to the understanding of dislocation-based strain hardening mechanisms in crystalline solids. Phase field model has shown great potential in modeling dislocation dynamics by both employing the continuum microelasticity theory to describe the elastic interactions and incorporating the γ-surface into the crystalline energy to enable the core reactions. Since the crystalline energy is approximately formulated by linear superposition of interplanar potential of each slip plane in the previous phase field model, it does not fully account for the reactions between dislocations gliding in intersecting slip planes. In this study, an improved phase field model of dislocation intersections is proposed through updating the crystalline energy by coupling the potential of two intersecting planes, and then applied to study the collinear interaction followed by comparison with the previous simulation result using discrete dislocation dynamics. Collinear annihilation captured only in the improved phase field model is found to strongly affect the junction formation and plastic flow in multislip systems. The results indicate that the improvement is essential for phase field model of dislocation intersections.
Functionalization of β-lactam antibiotic on lysozyme capped gold nanoclusters retrogress MRSA and its persisters following awakening
Authors: Kalita Sanjeeb , Kandimalla Raghuram , Bhowal Ashim Chandra , Kotoky Jibon , Kundu Sarathi
Published: April 2018

In this study we have reported an efficient antibacterial hybrid fabricated through surface functionalization of lysozyme capped gold nanoclusters (AUNC-L) with β-lactam antibiotic ampicillin (AUNC-L-Amp). The prepared hybrid not only reverted the MRSA resistance towards ampicillin but also demonstrated enhanced antibacterial activity against non-resistant bacterial strains. Most importantly, upon awakening through cis-2-decenoic acid (cis-DA) exposure, the MRSA persister got inhibited by the AUNC-L-Amp treatment. Intraperitoneal administration of this hybrid eliminates the systemic MRSA infection in a murine animal model. Topical application of this nano conjugate eradicated MRSA infection from difficult to treat diabetic wound of rat and accelerated the healing process. Due to inherent bio-safe nature of gold, AUNC-L alone or in the construct (AUNC-L-Amp) demonstrated excellent biocompatibility and did not indicate any deleterious effects in in vivo settings. We postulate that AUNC-L-Amp overcomes the elevated levels of β-lactamase at the site of MRSA antibiotic interaction with subsequent multivalent binding to the bacterial surface and enhanced permeation. Coordinated action of AUNC-L-Amp components precludes MRSA to attain resistance against the hybrid. We proposed that the inhibitory effect of AUNC-L-Amp against MRSA and its persister form is due to increased Amp concentration at the site of action, multivalent presentation and enhanced permeation of Amp through lysozyme-mediated cell wall lysis.
New Common and Rare Variants Influencing Metabolic Syndrome and Its Individual Components in a Korean Population
Authors: Lee Ho-Sun , Kim Yongkang , Park Taesung
Published: April 2018

To identify novel loci for susceptibility to MetS, we conducted genome-wide association and exome wide association studies consisting of a discovery stage cohort (KARE, 1946 cases and 6427 controls), and a replication stage cohort (HEXA, 430 cases and 3,264 controls). For finding genetic variants for MetS, with its components, we performed multivariate analysis for common and rare associations, using a standard logistic regression analysis for MetS. From the discovery and replication GWA studies, we confirmed 21 genome-wide signals significantly associated with MetS. Of these 21, four were previously unreported to associate with any MetS components: rs765547 near LPL; rs3782889 in MYL2; and rs11065756 and rs10849915 in CCDC63. Using exome chip variants, gene-based analysis of rare variants revealed three genes, CETP, SH2B1, and ZFP2, in the discovery stage, among which only CETP was confirmed in the replication stage. Finally, CETP D442G (rs2303790) associated, as a less common variant, with decreased risk of MetS. In conclusion, we discovered a total of five new MetS-associated loci, and their overlap with other disease-related components, suggest roles in the various etiologies of MetS, and its possible preventive strategies.
Positive Surgical Margins in the 10 Most Common Solid Cancers
Authors: Orosco Ryan K. , Tapia Viridiana J. , Califano Joseph A. , Clary Bryan , Cohen Ezra E. W. , Kane Christopher , Lippman Scott M. , Messer Karen , Molinolo Alfredo , Murphy James D. , Pang John , Sacco Assuntina , Tringale Kathryn R. , Wallace Anne , Nguyen Quyen T.
Published: April 2018

A positive surgical margin (PSM) following cancer resection oftentimes necessitates adjuvant treatments and carries significant financial and prognostic implications. We sought to compare PSM rates for the ten most common solid cancers in the United States, and to assess trends over time. Over 10 million patients were identified in the National Cancer Data Base from 1998–2012, and 6.5 million had surgical margin data. PSM rates were compared between two time periods, 1998–2002 and 2008–2012. PSM was positively correlated with tumor category and grade. Ovarian and prostate cancers had the highest PSM prevalence in women and men, respectively. The highest PSM rates for cancers affecting both genders were seen for oral cavity tumors. PSM rates for breast cancer and lung and bronchus cancer in both men and women declined over the study period. PSM increases were seen for bladder, colon and rectum, and kidney and renal pelvis cancers. This large-scale analysis appraises the magnitude of PSM in the United States in order to focus future efforts on improving oncologic surgical care with the goal of optimizing value and improving patient outcomes.
Author Correction: Analysis of inflammatory cytokine and TLR expression levels in Type 2 Diabetes with complications
Authors: Gupta Saket , Maratha Ashwini , Siednienko Jakub , Natarajan Anandan , Gajanayake Thusitha , Hoashi Shu , Miggin Sinéad
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Author Correction: Maximizing energy coupling to complex plasmonic devices by injecting light into eigenchannels
Authors: Jo Yonghyeon , Choi Wonjun , Seo Eunsung , Ahn Junmo , Park Q-Han , Jhon Young Min , Choi Wonshik
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Imaging beyond ultrasonically-impenetrable objects
Authors: Ilovitsh Tali , Ilovitsh Asaf , Foiret Josquin , Ferrara Katherine W.
Published: April 2018

Ultrasound images are severely degraded by the presence of obstacles such as bones and air gaps along the beam path. This paper describes a method for imaging structures that are distal to obstacles that are otherwise impenetrable to ultrasound. The method uses an optically-inspired holographic algorithm to beam-shape the emitted ultrasound field in order to bypass the obstacle and place the beam focus beyond the obstruction. The resulting performance depends on the transducer aperture, the size and position of the obstacle, and the position of the target. Improvement compared to standard ultrasound imaging is significant for obstacles for which the width is larger than one fourth of the transducer aperture and the depth is within a few centimeters of the transducer. For such cases, the improvement in focal intensity at the location of the target reaches 30-fold, and the improvement in peak-to-side-lobe ratio reaches 3-fold. The method can be implemented in conventional ultrasound systems, and the entire process can be performed in real time. This method has applications in the fields of cancer detection, abdominal imaging, imaging of vertebral structure and ultrasound tomography. Here, its effectiveness is demonstrated using wire targets, tissue mimicking phantoms and an ex vivo biological sample.
Contrasting epigenetic states of heterochromatin in the different types of mouse pluripotent stem cells
Authors: Tosolini Matteo , Brochard Vincent , Adenot Pierre , Chebrout Martine , Grillo Giacomo , Navia Violette , Beaujean Nathalie , Francastel Claire , Bonnet-Garnier Amélie , Jouneau Alice
Published: April 2018

Mouse embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs) represent naive and primed pluripotency states, respectively, and are maintained in vitro by specific signalling pathways. Furthermore, ESCs cultured in serum-free medium with two kinase inhibitors (2i-ESCs) are thought to be the ground naïve pluripotent state. Here, we present a comparative study of the epigenetic and transcriptional states of pericentromeric heterochromatin satellite sequences found in these pluripotent states. We show that 2i-ESCs are distinguished from other pluripotent cells by a prominent enrichment in H3K27me3 and low levels of DNA methylation at pericentromeric heterochromatin. In contrast, serum-containing ESCs exhibit higher levels of major satellite repeat transcription, which is lower in 2i-ESCs and even more repressed in primed EpiSCs. Removal of either DNA methylation or H3K9me3 at PCH in 2i-ESCs leads to enhanced deposition of H3K27me3 with few changes in satellite transcript levels. In contrast, their removal in EpiSCs does not lead to deposition of H3K27me3 but rather removes transcriptional repression. Altogether, our data show that the epigenetic state of PCH is modified during transition from naive to primed pluripotency states towards a more repressive state, which tightly represses the transcription of satellite repeats.
Retraction of the dissolution front in natural porous media
Authors: Yang Y. , Bruns S. , Rogowska M. , Hakim S. S. , Hammel J. U. , Stipp S. L. S. , Sørensen H. O.
Published: April 2018

The dissolution of porous materials in a flow field controls the fluid pathways through rocks and soils and shapes the morphology of landscapes. Identifying the dissolution front, the interface between the reactive and the unreactive volumes in a dissolving medium, is a prerequisite for describing dissolution-induced structure emergence and transformation. Despite its fundamental importance, the report on the dynamics of a dissolution front in an evolving natural microstructure is scarce. Here we show an unexpected, spontaneous migration of the dissolution front against the flow direction. This retraction stems from infiltration instability induced surface generation, which leads to an increase in reactive surface area when a porous medium dissolves in an imposing flow field. There is very good agreement between observations made with in situ, X-ray tomography and model predictions. Both show that the value of reactive surface area reflects a balance between flow-dependent surface generation and destruction, i.e. the “dry” geometric surface area of a porous material, measured without a flow field, is not necessarily the upper limit of its reactive surface area when in contact with reactive flow. This understanding also contributes to reconciling the discrepancies between field and laboratory derived solid-fluid reaction kinetics.
Correcting B0 Field Distortions in MRI Caused by Stainless Steel Orthodontic Appliances at 1.5 T Using Permanent Magnets – A Head Phantom Study
Authors: Wang Zhiyue J. , Park Yong Jong , Morriss Michael C. , Seo Youngseob , Nguyen Trung , Hallac Rami R. , Nava Ana , Chopra Rajiv , Chatzinoff Yonatan , Price Khyana , Rollins Nancy K.
Published: April 2018

Susceptibility artifacts caused by stainless steel orthodontic appliances (braces) pose significant challenges in clinical brain MRI examinations. We introduced field correction device (FCD) utilizing permanent magnets to cancel the induced B0inhomogeneity and mitigate geometric distortions in MRI. We evaluated a prototype FCD using a 3D-printed head phantom in this proof of concept study. The phantom was compartmented into anterior frontal lobe, temporal lobe, fronto-parieto-occipital lobe, basal ganglia and thalami, brain stem, and cerebellum and had built-in orthogonal gridlines to facilitate the quantification of geometric distortions and volume obliterations. Stainless steel braces were mounted on dental models of three different sizes with total induced magnetic moment 0.15 to 0.17 A·m2. With braces B0standard deviation (SD) ranged from 2.8 to 3.7 ppm in the temporal and anterior frontal lobes vs. 0.2 to 0.3 ppm without braces. The volume of brain regions in diffusion weighted imaging was obliterated by 32–38% with braces vs. 0% without braces in the cerebellum. With the FCD the SD of B0ranged from 0.3 to 1.2 ppm, and obliterated volume ranged from 0 to 6% in the corresponding brain areas. These results showed that FCD can effectively decrease susceptibility artifacts from orthodontic appliances.
Ion Permeation Mechanism in Epithelial Calcium Channel TRVP6
Authors: Sakipov Serzhan , Sobolevsky Alexander I. , Kurnikova Maria G.
Published: April 2018

Calcium is the most abundant metal in the human body that plays vital roles as a cellular electrolyte as well as the smallest and most frequently used signaling molecule. Calcium uptake in epithelial tissues is mediated by tetrameric calcium-selective transient receptor potential (TRP) channels TRPV6 that are implicated in a variety of human diseases, including numerous forms of cancer. We used TRPV6 crystal structures as templates for molecular dynamics simulations to identify ion binding sites and to study the permeation mechanism of calcium and other ions through TRPV6 channels. We found that at low Ca2+ concentrations, a single calcium ion binds at the selectivity filter narrow constriction formed by aspartates D541 and allows Na+ permeation. In the presence of ions, no water binds to or crosses the pore constriction. At high Ca2+ concentrations, calcium permeates the pore according to the knock-off mechanism that includes formation of a short-lived transition state with three calcium ions bound near D541. For Ba2+, the transition state lives longer and the knock-off permeation occurs slower. Gd3+ binds at D541 tightly, blocks the channel and prevents Na+ from permeating the pore. Our results provide structural foundations for understanding permeation and block in tetrameric calcium-selective ion channels.
Effects of oil-film layer and surfactant on the siphonal respiration and survivorship in the fourth instar larvae of Aedes togoi mosquito in laboratory conditions
Authors: Lee Sang Joon , Kim Jun Ho , Lee Seung Chul
Published: April 2018

Mosquitoes transmit various diseases; thus, controlling them is necessary to prevent mosquito-borne infections. Unlike flying adult mosquitoes, those in the immature stages are easy to control because of being restricted to their habitats found in an aquatic environment. In this study, we aimed to evaluate of respiration and survivorship in the larvae of Aedes togoi. The mechanism of actions of the oil-film layer and the surfactant as well as their effects on the siphonal respiration of submerged Aedes togoi larvae were analyzed by checking the survival time of mosquito larvae against oil-film layer and surfactant, and conducting experiments using a siphon-model. Compared with an impermeable membrane used for reference (762.4 min; average time in all cases), the survival time of mosquito larvae was 5% longer for the oil-film layer (808.1 min) and 40% longer for the surfactant (1086.9 min). The surface of the siphon was changed from hydrophobic to hydrophilic by addition of a surfactant. In addition, the surface tension and wettability have a significant influence on the opening and closing of siphon. This study would be helpful for understanding the basic mechanism of physical control measures for disturbing the siphonal respiration of mosquito larvae in a way of dissolved oxygen and surface tension. The present results would guide the establishment of effective control measures for mosquitoes.
Metabolomics and proteomics reveal drought-stress responses of leaf tissues from spring-wheat
Authors: Michaletti Anna , Naghavi Mohammad Reza , Toorchi Mahmoud , Zolla Lello , Rinalducci Sara
Published: April 2018

To reveal the integrative biochemical networks of wheat leaves in response to water deficient conditions, proteomics and metabolomics were applied to two spring-wheat cultivars (Bahar, drought-susceptible; Kavir, drought-tolerant). Drought stress induced detrimental effects on Bahar leaf proteome, resulting in a severe decrease of total protein content, with impairments mainly in photosynthetic proteins and in enzymes involved in sugar and nitrogen metabolism, as well as in the capacity of detoxifying harmful molecules. On the contrary, only minor perturbations were observed at the protein level in Kavir stressed leaves. Metabolome analysis indicated amino acids, organic acids, and sugars as the main metabolites changed in abundance upon water deficiency. In particular, Bahar cv showed increased levels in proline, methionine, arginine, lysine, aromatic and branched chain amino acids. Tryptophan accumulation via shikimate pathway seems to sustain auxin production (indoleacrylic acid), whereas glutamate reduction is reasonably linked to polyamine (spermine) synthesis. Kavir metabolome was affected by drought stress to a less extent with only two pathways significantly changed, one of them being purine metabolism. These results comprehensively provide a framework for better understanding the mechanisms that govern plant cell response to drought stress, with insights into molecules that can be used for crop improvement projects.
Growth mechanism of epitaxial YSZ on Si by Pulsed Laser Deposition
Authors: Dubbink David , Koster Gertjan , Rijnders Guus
Published: April 2018

The epitaxial growth of yttria-stabilized zirconia (YSZ) on silicon with native oxide was investigated in order to gain more insight in the growth mechanism. Specifically, attention was paid to the possibilities to control the chemical interactions between YSZ, silicon and oxygen during initial growth. The sources of oxygen during growth proved to play an important role in the growth process, as shown by individual manipulation of all sources present during Pulsed Laser Deposition. Partial oxidation of the YSZ plasma and sufficient delivery of oxygen to the growing film were necessary to prevent silicide formation and obtain optimal YSZ crystalline qualities. In these conditions, thickness increase of the silicon native oxide before growth just started to occur, while a much faster regrowth of silicon oxide at the YSZ-Si interface occurred during growth. Control of all these contributions to the growth process is necessary to obtain reproducible growth of high quality YSZ.
Temporal and spatial changes of macrobenthos community in the regions frequently occurring black water aggregation in Lake Taihu
Authors: Chen Jianqin , Hu Dongfang , Zhang Chenling , Ding Zhengfeng
Published: April 2018

Seasonal survey was performed from August 2015 to May 2016 at 50 sampling sites in Lake Taihu to determine the spatial and temporal changes in macrobenthos community and their relationships with environmental variables. A total of 58 macrobenthos species were collected and identified, including 28 species of annelids, 17 species of molluscs, and 12 species of arthropods. Both the community composition and the dominant species changed temporally and spatially. Correspondingly, the macrobenthos biodiversity differed among regions and seasons. The macrobenthos density decreased with increased sediment depth, which is the first report about the vertical distribution of macrobenthos in Lake Taihu. The majority of benthic animals were located within the sediment depth of 0–5 cm and 5–10 cm, accounting for 39.25% and 24.87% of the total abundance respectively. Redundancy discriminate analysis revealed that the main environmental factors affecting the most contributing macrobenthos species were temperature in summer, transparency, dissolved oxygen and pH in autumn, and water depth and dissolved oxygen in winter. Particularly, salinity and conductivity showed high correlation with the macrobenthos community through the whole sampling period. The investigation reveals the inherent spatiotemporal variation of macrobenthos community, and provides references for the biological assessment of water quality in Lake Taihu.