bluuebunny/crossref_metadata_2025 huggingface dataset:
Lithospheric Control on Asthenospheric Flow From the Iceland Plume: 3‐D Density Modeling of the Jan Mayen‐East Greenland Region, NE Atlantic
Authors: Tan Pingchuan , Sippel Judith , Breivik Asbjørn Johan , Meeßen Christian , Scheck‐Wenderoth Magdalena
Published: September 2018

The density structure of the oceanic lithosphere north of Iceland is key for understanding the effects of the Iceland plume on the greater Jan Mayen‐East Greenland Region. We obtain the 3‐D density structure of the sediments and the crust from regional reflection and refraction seismic lines. The temperature and related density structures of the mantle between 50 and 250 km are derived from a shear wave velocity (Vs) tomography model. To assess the density between the Moho and 50‐km depth, we combine forward and inverse 3‐D gravity modeling. Beneath the Middle Kolbeinsey Ridge (MKR) region, a deep, broad negative mantle density anomaly occurs under the Kolbeinsey Ridge. It is overlain by a narrower uppermost mantle NE‐SW elongated negative density anomaly, which is increasingly displaced eastward of the spreading axis northward. It crosses the West Jan Mayen Fracture Zone and becomes weaker approaching the Mohn's spreading ridge. The effect of this anomaly is consistent with significantly shallower basement on the eastern side of the MKR. We interpret this as the result of thermal erosion of the lithosphere by hot asthenospheric flow out from the Iceland plume, possibly the main driver for several eastward jumps of the MKR during the last 5.5 Ma. The cause for the deviation of the flow may be that the West Jan Mayen Fracture Zone is easier to cross in a region where the difference in lithospheric thickness is small. That implies that the bottom lithospheric topography exerts a regional but not local influence on upper asthenospheric flow.
Housing Age and Affluence Influence Plant and Soil Nitrogen and Carbon Cycles in Two Semiarid Cities
Authors: Cobley L. A. E. , Pataki D. E. , McCarthy H. R. , Martin S. A. , Ehleringer J. R.
Published: September 2018

While human activities have altered the urban nitrogen (N) and carbon (C) cycles, the relationships between social and biophysical processes in cities are not well understood. Here we evaluated relationships between sociodemographic variables (median household income and housing age) and N and C contents and stable isotope ratios of vegetation in the Los Angeles Metropolitan Area (LA), California, and the Salt Lake Valley, Utah. We hypothesized that (1) N content and stable isotope ratios would be negatively related to income via increased N deposition in lower‐income areas; (2) N and C content and N stable isotope ratios would have a positive relationship with age due to soil organic matter accumulation and increased exposure to N losses over time, respectively; and (3) δ13C would increase with income as a result of increased fossil fuel‐derived CO2concentrations in lower‐income areas. We found that δ15N values decreased with median household income in both cities and N content decreased with income in LA. In addition, atmospheric NO2concentrations decreased with income in LA. Soil N and C content increased with housing age. However, δ15N had opposing relationships with age in the two cities. Finally, foliar δ13C values were more isotopically depleted with both increasing household income and increasing NO2concentrations in LA. These results show that urban foliar and soil isotopic composition are associated with sociodemographic variables and that affluence, as well as housing age, influences urban plant and soil function.
The Extent and Regulation of Summer Methane Oxidation in Northern Lakes
Authors: Thottathil Shoji D. , Reis Paula C. J. , del Giorgio Paul A. , Prairie Yves T.
Published: September 2018

Inland waters have a significant influence on atmospheric methane (CH4) levels. However, processes determining the strength of CH4 emissions from these systems are not well defined. Aerobic oxidation is a major sink of CH4 in freshwater environments and thus an important determinant of aquatic CH4 emissions, yet strikingly little is known about its drivers. Here we assessed the extent of water column CH4 oxidation at the whole ecosystem scale using stable carbon isotopic (δ13C) mass balance of CH4 in 14 northern lakes spanning wide range of dissolved organic carbon (DOC) concentrations. We show that the extent of oxidation can vary from near zero to near complete, and for concentrations of 1.9–11 mg/L, DOC is a key modulator of CH4 oxidation during the summer stratification period. Increasing DOC concentrations enhances oxidation in the upper layers by reducing light inhibition on methanotrophic activity, while reducing oxygen available for oxidation in the deeper layers. The effect of this light inhibition was also observable over the diurnal cycle. We developed simple predictive empirical models (r2 > 0.82) to estimate the extent of oxidation in the different layers of lakes for the summer period. Applying our surface layer model to a larger data set suggests that about 30% of CH4 transported to or generated within the epilimnion of Québec lakes is oxidized during summer. Our results imply that DOC concentration, through its effect on the light regime of lakes, has the potential to affect strongly the magnitude and patterns of summer CH4 emissions.
Oxygen Transfer at the Sediment/Water Interface for Sediment Bed With Rough Surface
Authors: Higashino Makoto
Published: September 2018

A model of sediment oxygen demand (SOD) for a sediment bed with a rough surface was presented. The equivalent sand roughness commonly used in hydraulics was chosen to express the size of roughness elements, and SOD was expressed as a function of the intensity of near‐bed turbulence described by the shear velocity; microbial oxygen uptake rate, that is, the maximum oxidation rate; and roughness height. The modeling results show that bed roughness enhances oxygen transfer from the water column to the sediment surface. The effects of bed roughness on SOD depend on both the shear velocity and microbial oxygen uptake rate. At low microbial oxygen uptake rate, SOD approaches a constant value rapidly as the shear velocity increases. Bed roughness barely influences SOD regardless of the shear velocity because SOD can substantially besediment side limiting. The roughness height plays an important role in determining SOD at high microbial oxygen uptake rate, because SOD can be controlled by oxygen transfer from the water column to the sediment surface, that is,transfer limiting. Increasing roughness height makes the oxygen transfer rate from flowing water to the sediment surface faster as well as increasing shear velocity, resulting in raised SOD. The proposed mode can substantially reproduce the experimental SOD for rough bed.
PAXX and its paralogs synergistically direct DNA polymerase λ activity in DNA repair
Authors: Craxton Andrew , Munnur Deeksha , Jukes-Jones Rebekah , Skalka George , Langlais Claudia , Cain Kelvin , Malewicz Michal
Published: September 2018

PAXX is a recently identified component of the nonhomologous end joining (NHEJ) DNA repair pathway. The molecular mechanisms of PAXX action remain largely unclear. Here we characterise the interactomes of PAXX and its paralogs, XLF and XRCC4, to show that these factors share the ability to interact with DNA polymerase λ (Pol λ), stimulate its activity and are required for recruitment of Pol λ to laser-induced DNA damage sites. Stimulation of Pol λ activity by XRCC4 paralogs requires a direct interaction between the SP/8 kDa domain of Pol λ and their N-terminal head domains to facilitate recognition of the 5′ end of substrate gaps. Furthermore, PAXX and XLF collaborate with Pol λ to promote joining of incompatible DNA ends and are redundant in supporting Pol λ function in vivo. Our findings identify Pol λ as a novel downstream effector of PAXX function and show XRCC4 paralogs act in synergy to regulate polymerase activity in NHEJ.
BRWD1 orchestrates epigenetic landscape of late B lymphopoiesis
Authors: Mandal Malay , Maienschein-Cline Mark , Maffucci Patrick , Veselits Margaret , Kennedy Domenick E. , McLean Kaitlin C. , Okoreeh Michael K. , Karki Sophiya , Cunningham-Rundles Charlotte , Clark Marcus R.
Published: September 2018

Transcription factor (TF) networks determine cell fate in hematopoiesis. However, how TFs cooperate with other regulatory mechanisms to instruct transcription remains poorly understood. Here we show that in small pre-B cells, the lineage restricted epigenetic reader BRWD1 closes early development enhancers and opens the enhancers of late B lymphopoiesis to TF binding. BRWD1 regulates over 7000 genes to repress proliferative and induce differentiation programs. However, BRWD1 does not regulate the expression of TFs required for B lymphopoiesis. Hypogammaglobulinemia patients with BRWD1 mutations have B-cell transcriptional profiles and enhancer landscapes similar to those observed in Brwd1-/- mice. These data indicate that, in both mice and humans, BRWD1 is a master orchestrator of enhancer accessibility that cooperates with TF networks to drive late B-cell development.
Towards exact molecular dynamics simulations with machine-learned force fields
Authors: Chmiela Stefan , Sauceda Huziel E. , Müller Klaus-Robert , Tkatchenko Alexandre
Published: September 2018

Molecular dynamics (MD) simulations employing classical force fields constitute the cornerstone of contemporary atomistic modeling in chemistry, biology, and materials science. However, the predictive power of these simulations is only as good as the underlying interatomic potential. Classical potentials often fail to faithfully capture key quantum effects in molecules and materials. Here we enable the direct construction of flexible molecular force fields from high-level ab initio calculations by incorporating spatial and temporal physical symmetries into a gradient-domain machine learning (sGDML) model in an automatic data-driven way. The developed sGDML approach faithfully reproduces global force fields at quantum-chemical CCSD(T) level of accuracy and allows converged molecular dynamics simulations with fully quantized electrons and nuclei. We present MD simulations, for flexible molecules with up to a few dozen atoms and provide insights into the dynamical behavior of these molecules. Our approach provides the key missing ingredient for achieving spectroscopic accuracy in molecular simulations.
Contrasting effects on deep convective clouds by different types of aerosols
Authors: Jiang Jonathan H. , Su Hui , Huang Lei , Wang Yuan , Massie Steven , Zhao Bin , Omar Ali , Wang Zhien
Published: September 2018

Convective clouds produce a significant proportion of the global precipitation and play an important role in the energy and water cycles. We quantify changes of the convective cloud ice mass-weighted altitude centroid (ZIWC) as a function of aerosol optical thickness (AOT). Analyses are conducted in smoke, dust and polluted continental aerosol environments over South America, Central Africa and Southeast Asia, using the latest measurements from the CloudSat and CALIPSO satellites. We find aerosols can inhibit or invigorate convection, depending on aerosol type and concentration. On average, smoke tends to suppress convection and results in lower ZIWC than clean clouds. Polluted continental aerosol tends to invigorate convection and promote higher ZIWC. The dust aerosol effects are regionally dependent and their signs differ from place to place. Moreover, we find that the aerosol inhibition or invigoration effects do not vary monotonically with AOT and the variations depend strongly on aerosol type. Our observational findings indicate that aerosol type is one of the key factors in determining the aerosol effects on convective clouds.
Acquired cancer resistance to combination immunotherapy from transcriptional loss of class I HLA
Authors: Paulson K. G. , Voillet V. , McAfee M. S. , Hunter D. S. , Wagener F. D. , Perdicchio M. , Valente W. J. , Koelle S. J. , Church C. D. , Vandeven N. , Thomas H. , Colunga A. G. , Iyer J. G. , Yee C. , Kulikauskas R. , Koelle D. M. , Pierce R. H. , Bielas J. H. , Greenberg P. D. , Bhatia S. , Gottardo R. , Nghiem P. , Chapuis A. G.
Published: September 2018

Understanding mechanisms of late/acquired cancer immunotherapy resistance is critical to improve outcomes; cellular immunotherapy trials offer a means to probe complex tumor–immune interfaces through defined T cell/antigen interactions. We treated two patients with metastatic Merkel cell carcinoma with autologous Merkel cell polyomavirus specific CD8+ T cells and immune-checkpoint inhibitors. In both cases, dramatic remissions were associated with dense infiltration of activated CD8+s into the regressing tumors. However, late relapses developed at 22 and 18 months, respectively. Here we report single cell RNA sequencing identified dynamic transcriptional suppression of the specific HLA genes presenting the targeted viral epitope in the resistant tumor as a consequence of intense CD8-mediated immunologic pressure; this is distinguished from genetic HLA-loss by its reversibility with drugs. Transcriptional suppression of Class I loci may underlie resistance to other immunotherapies, including checkpoint inhibitors, and have implications for the design of improved immunotherapy treatments.
Eosinophil recruitment is dynamically regulated by interplay among lung dendritic cell subsets after allergen challenge
Authors: Yi Shuying , Zhai Jing , Niu Rui , Zhu Guangming , Wang Meixiang , Liu Jianguo , Huang Hua , Wang Yaping , Jing Xiuli , Kang Li , Song Wengang , Shi Yufang , Tang Hua
Published: September 2018

Eosinophil infiltration, a hallmark of allergic asthma, is essential for type 2 immune responses. How the initial eosinophil recruitment is regulated by lung dendritic cell (DC) subsets during the memory stage after allergen challenge is unclear. Here, we show that the initial eosinophil infiltration is dependent on lung cDC1s, which require nitric oxide (NO) produced by inducible NO synthase from lung CD24−CD11b+DC2s for inducing CCL17 and CCL22 to attract eosinophils. During late phase responses after allergen challenge, lung CD24+cDC2s inhibit eosinophil recruitment through secretion of TGF-β1, which impairs the expression of CCL17 and CCL22. Our data suggest that different lung antigen-presenting cells modulate lung cDC1-mediated eosinophil recruitment dynamically, through secreting distinct soluble factors during the memory stage of chronic asthma after allergen challenge in the mouse.
Identifying the missing link in catalyst transfer polymerization
Authors: He Weiying , Patrick Brian O. , Kennepohl Pierre
Published: September 2018

Nickel-catalyzed catalyst transfer polycondensation (CTP) of thiophenes is an efficient strategy for the controlled synthesis of polythiophenes. However, a detailed view of its reaction mechanism has remained elusive with unresolved questions regarding the geometry and bonding of critical Ni(0) thiophene intermediates. Herein, we provide experimental and computational evidence of structurally characterized square planar η2-Ni(0)–thiophene species and their relevance to the mechanism of CTP. These results confirm the viability of C,C-η2 bound intermediates in CTP of thiophenes, providing an electronic rationale for the stability of such species, and thus that such processes can proceed as living polymerizations. We further show that C,S-κ2 species may also be relevant in nickel-catalyzed CTP of thiophenes, providing new avenues for exploitation and optimization.
Microfluidic deposition for resolving single-molecule protein architecture and heterogeneity
Authors: Ruggeri Francesco Simone , Charmet Jerome , Kartanas Tadas , Peter Quentin , Chia Sean , Habchi Johnny , Dobson Christopher M. , Vendruscolo Michele , Knowles Tuomas P. J.
Published: September 2018

Scanning probe microscopy provides a unique window into the morphology, mechanics, and structure of proteins and their complexes on the nanoscale. Such measurements require, however, deposition of samples onto substrates. This process can affect conformations and assembly states of the molecular species under investigation and can bias the molecular populations observed in heterogeneous samples through differential adsorption. Here, we show that these limitations can be overcome with a single-step microfluidic spray deposition platform. This method transfers biological solutions to substrates as microdroplets with subpicoliter volume, drying in milliseconds, a timescale that is shorter than typical diffusion times of proteins on liquid–solid interfaces, thus avoiding surface mass transport and change to the assembly state. Finally, the single-step deposition ensures the attachment of the full molecular content of the sample to the substrate, allowing quantitative measurements of different molecular populations within heterogeneous systems, including protein aggregates.
Neurogenetic profiles delineate large-scale connectivity dynamics of the human brain
Authors: Diez Ibai , Sepulcre Jorge
Published: September 2018

Experimental and modeling work of neural activity has described recurrent and attractor dynamic patterns in cerebral microcircuits. However, it is still poorly understood whether similar dynamic principles exist or can be generalizable to the large-scale level. Here, we applied dynamic graph theory-based analyses to evaluate the dynamic streams of whole-brain functional connectivity over time across cognitive states. Dynamic connectivity in local networks is located in attentional areas during tasks and primary sensory areas during rest states, and dynamic connectivity in distributed networks converges in the default mode network (DMN) in both task and rest states. Importantly, we find that distinctive dynamic connectivity patterns are spatially associated with Allen Human Brain Atlas genetic transcription levels of synaptic long-term potentiation and long-term depression-related genes. Our findings support the neurobiological basis of large-scale attractor-like dynamics in the heteromodal cortex within the DMN, irrespective of cognitive state.
Griffithsin carrageenan fast dissolving inserts prevent SHIV HSV-2 and HPV infections in vivo
Authors: Derby Nina , Lal Manjari , Aravantinou Meropi , Kizima Larisa , Barnable Patrick , Rodriguez Aixa , Lai Manshun , Wesenberg Asa , Ugaonkar Shweta , Levendosky Keith , Mizenina Olga , Kleinbeck Kyle , Lifson Jeffrey D. , Peet M. Melissa , Lloyd Zachary , Benson Michael , Heneine Walid , O’Keefe Barry R , Robbiani Melissa , Martinelli Elena , Grasperge Brooke , Blanchard James , Gettie Agegnehu , Teleshova Natalia , Fernández-Romero José A. , Zydowsky Thomas M.
Published: September 2018

Human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) strategies with proven in vivo efficacy rely on antiretroviral drugs, creating the potential for drug resistance and complicated treatment options in individuals who become infected. Moreover, on-demand products are currently missing from the PrEP development portfolio. Griffithsin (GRFT) is a non-antiretroviral HIV entry inhibitor derived from red algae with an excellent safety profile and potent activity in vitro. When combined with carrageenan (CG), GRFT has strong activity against herpes simplex virus-2 (HSV-2) and human papillomavirus (HPV) in vitro and in vivo. Here, we report that GRFT/CG in a freeze-dried fast dissolving insert (FDI) formulation for on-demand use protects rhesus macaques from a high dose vaginal SHIV SF162P3 challenge 4 h after FDI insertion. Furthermore, the GRFT/CG FDI also protects mice vaginally against HSV-2 and HPV pseudovirus. As a safe, potent, broad-spectrum, on-demand non-antiretroviral product, the GRFT/CG FDI warrants clinical development.
Regulation of the terminal maturation of iNKT cells by mediator complex subunit 23
Authors: Xu Yu , Sun Yang , Shen Hao , Dai Yuling , Liu Haifeng , Li Ronghong , Zhang Hongdao , Wu Ligang , Zhu Xiaoyan , Liu Xiaolong
Published: September 2018

Invariant natural killer T cells (iNKT cells) are a specific subset of T cells that recognize glycolipid antigens and upon activation rapidly exert effector functions. This unique function is established during iNKT cell development; the detailed mechanisms of this process, however, remain to be elucidated. Here the authors show that deletion of the mediator subunit Med23 in CD4+CD8+double positive (DP) thymocytes completely blocks iNKT cell development at stage 2. This dysregulation is accompanied by a bias in the expression of genes related to the regulation of transcription and metabolism, and functional impairment of the cells including the loss of NK cell characteristics, reduced ability to secrete cytokines and attenuated recruitment capacity upon activation. Moreover,Med23-deficient iNKT cells exhibit impaired anti-tumor activity. Our study identifies Med23 as an essential transcriptional regulator that controls iNKT cell differentiation and terminal maturation.
Maternal gut and breast milk microbiota affect infant gut antibiotic resistome and mobile genetic elements
Authors: Pärnänen Katariina , Karkman Antti , Hultman Jenni , Lyra Christina , Bengtsson-Palme Johan , Larsson D. G. Joakim , Rautava Samuli , Isolauri Erika , Salminen Seppo , Kumar Himanshu , Satokari Reetta , Virta Marko
Published: September 2018

The infant gut microbiota has a high abundance of antibiotic resistance genes (ARGs) compared to adults, even in the absence of antibiotic exposure. Here we study potential sources of infant gut ARGs by performing metagenomic sequencing of breast milk, as well as infant and maternal gut microbiomes. We find that fecal ARG and mobile genetic element (MGE) profiles of infants are more similar to those of their own mothers than to those of unrelated mothers. MGEs in mothers’ breast milk are also shared with their own infants. Termination of breastfeeding and intrapartum antibiotic prophylaxis of mothers, which have the potential to affect microbial community composition, are associated with higher abundances of specific ARGs, the composition of which is largely shaped by bacterial phylogeny in the infant gut. Our results suggest that infants inherit the legacy of past antibiotic consumption of their mothers via transmission of genes, but microbiota composition still strongly impacts the overall resistance load.
Modulating the hierarchical fibrous assembly of Au nanoparticles with atomic precision
Authors: Li Qi , Russell Jake C. , Luo Tian-Yi , Roy Xavier , Rosi Nathaniel L. , Zhu Yan , Jin Rongchao
Published: September 2018

The ability to modulate nanoparticle (NP) assemblies with atomic precision is still lacking, which hinders us from creating hierarchical NP organizations with desired properties. In this work, a hierarchical fibrous (1D to 3D) assembly of Au NPs (21-gold atom, Au21) is realized and further modulated with atomic precision via site-specific tailoring of the surface hook (composed of four phenyl-containing ligands with a counteranion). Interestingly, tailoring of the associated counterion significantly changes the electrical transport properties of the NP-assembled solids by two orders of magnitude due to the altered configuration of the interacting π–π pairs of the surface hooks. Overall, our success in atomic-level modulation of the hierarchical NP assembly directly evidences how the NP ligands and associated counterions can function to guide the 1D, 2D, and 3D hierarchical self-assembly of NPs in a delicate manner. This work expands nanochemists’ skills in rationally programming the hierarchical NP assemblies with controllable structures and properties.
Atom-hybridization for synthesis of polymetallic clusters
Authors: Tsukamoto Takamasa , Kambe Tetsuya , Nakao Aiko , Imaoka Takane , Yamamoto Kimihisa
Published: September 2018

The chemistry of metal clusters on the sub-nanometer scale is not yet well understood because metal clusters, especially multimetallic clusters, are difficult to synthesize with control over size and composition. The template synthesis of multimetallic sub-nanoclusters is achieved using a phenylazomethine dendrimer as a macromolecular template. Its intramolecular potential gradient allows the precise uptake of metal precursor complexes containing up to eight elements on the template. The usefulness of this method is demonstrated by synthesizing multimetallic sub-nanoclusters composed of five elements (Ga1In1Au3Bi2Sn6). The size and composition of this cluster can be precisely controlled and the metals involved are alloyed with each other. This approach provides the ability to easily blend different metals in various combinations to create new materials on the sub-nanometer scale, which will lead to the development of a new area in the field of chemistry.
Identification of Quantitative Trait Loci and Candidate Genes for Maize Starch Granule Size through Association Mapping
Authors: Liu Na , Zhang Zhanhui , Xue Yadong , Meng Shujun , Huang Yubi , Li Weihua , Huang Jihong , Tang Jihua
Published: September 2018

Starch is an important nutrient component of maize kernels, and starch granule size largely determines kernel waxiness, viscosity, and other physiochemical and processing properties. To explore the genetic basis of maize starch granule size, 266 tropical, subtropical, and temperate inbred lines were subjected to genome-wide association analyses with an array of 56,110 random single nucleotide polymorphisms (SNPs). In the present panel, the kernel starch granule size ranged from 7–15.8 µm long and 6.8–14.3 µm wide. Fourteen significant SNPs were identified as being associated with the length of starch granules and 9 with their width. One linkage disequilibrium block flanking both sides of a significant SNP was defined as a quantitative trait locus (QTL) interval, and seven QTLs were mapped for both granule length and width. A total of 79 and 88 candidate genes associated with starch length and width, respectively, were identified as being distributed on QTL genomic regions. Among these candidate genes, six with high scores were predicted to be associated with maize starch granule size. A candidate gene association analysis identified significant SNPs within genes GRMZM2G419655 and GRMZM2G511067, which could be used as functional markers in screening starch granule size for different commercial uses.
Publisher Correction: Antiretroviral Drugs Alter the Content of Extracellular Vesicles from HIV-1-Infected Cells
Authors: DeMarino Catherine , Pleet Michelle L. , Cowen Maria , Barclay Robert A. , Akpamagbo Yao , Erickson James , Ndembi Nicaise , Charurat Manhattan , Jumare Jibreel , Bwala Sunday , Alabi Peter , Hogan Max , Gupta Archana , Noren Hooten Nicole , Evans Michele K. , Lepene Benjamin , Zhou Weidong , Caputi Massimo , Romerio Fabio , Royal Walter , El-Hage Nazira , Liotta Lance A. , Kashanchi Fatah
Published: September 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Dot-Matrix Hologram Rendering Algorithm and its Validation through Direct Laser Interference Patterning
Authors: Tamulevičius Tomas , Juodėnas Mindaugas , Klinavičius Tomas , Paulauskas Andrius , Jankauskas Kęstutis , Ostreika Armantas , Žutautas Andrius , Tamulevičius Sigitas
Published: September 2018

The fight against forgery of valuable items demands efficient and reasonably priced solutions. A security tag featuring holographic elements for anti-counterfeiting is one of them. However, the content and colours of a diffraction image that would be seen by an observer are often counterintuitive in the design stage. Here, we propose an original algorithm based on the conical diffraction formalism, which can be used to describe the variations of a diffraction image with respect to all aspects of observation. We validate the output of the algorithm by comparing it to test holograms, which we have produced by employing direct laser interference patterning (DLIP) in electrochemically grown nickel foil. We have employed a motorized femtosecond laser system to micro-machine arrays of 65 µm × 65 µm sized diffraction gratings with a defined orientation and pitch on the order of 1 µm. Based on completed diffraction efficiency measurements, we determined optimal ablation parameters, i.e. 57.4 mJ/cm2 fluence per pulse and 1100 pulses/pixel. Furthermore, we show how accurate the proposed algorithm is through measured diffraction spectra as well as captured diffraction images of test holograms produced using the obtained parameters. Finally, we showcase anti-counterfeiting tag prototypes with complex holographic effects, i.e. colour reconstruction, animation effects, and image multiplexing. The proposed algorithm can severely shorten the time between design and production of a holographic tag, especially when realizing it via a competitive origination technology—DLIP.
Development of a genome-informed loop-mediated isothermal amplification assay for rapid and specific detection of Xanthomonas euvesicatoria
Authors: Larrea-Sarmiento Adriana , Dhakal Upasana , Boluk Gamze , Fatdal Lilly , Alvarez Anne , Strayer-Scherer Amanda , Paret Mathews , Jones Jeff , Jenkins Daniel , Arif Mohammad
Published: September 2018

Bacterial spot (BS), caused by Xanthomonas euvesicatoria, X. vesicatoria, X. gardneri and X. perforans, is an economically important bacterial disease of tomato and pepper. Symptoms produced by all four species are nearly indistinguishable. At present, no point-of-care diagnostics exist for BS. In this research, we examined genomes of X. euvesicatoria, X. vesicatoria, X. gardneri, X. perforans and other species of Xanthomonas; the unique gene recG was chosen to design primers to develop a loop-mediated isothermal amplification (LAMP) assay to rapidly and accurately identify and differentiate X. euvesicatoria from other BS causing Xanthomonas sp. using a field-deployable portable BioRangerTM instrument. Specificity of the developed assay was tested against 39 strains of X. euvesicatoria and 41 strains of other species in inclusivity and exclusivity panels, respectively. The assay detection limit was 100 fg (~18 genome copies) of genomic DNA and 1,000 fg in samples spiked with tomato DNA. The assay unambiguously detected X. euvesicatoria in infected tomato plant samples. Concordant results were obtained when multiple operators performed the test independently. No false positives and false negatives were detected. The developed LAMP assay has numerous applications in diagnostics, biosecurity and disease management.
GWAS and eQTL analysis identifies a SNP associated with both residual feed intake and GFRA2 expression in beef cattle
Authors: Higgins Marc G. , Fitzsimons Claire , McClure Matthew C. , McKenna Clare , Conroy Stephen , Kenny David A. , McGee Mark , Waters Sinéad M. , Morris Derek W.
Published: September 2018

Residual feed intake (RFI), a measure of feed efficiency, is an important economic and environmental trait in beef production. Selection of low RFI (feed efficient) cattle could maintain levels of production, while decreasing feed costs and methane emissions. However, RFI is a difficult and expensive trait to measure. Identification of single nucleotide polymorphisms (SNPs) associated with RFI may enable rapid, cost effective genomic selection of feed efficient cattle. Genome-wide association studies (GWAS) were conducted in multiple breeds followed by meta-analysis to identify genetic variants associated with RFI and component traits (average daily gain (ADG) and feed intake (FI)) in Irish beef cattle (n = 1492). Expression quantitative trait loci (eQTL) analysis was conducted to identify functional effects of GWAS-identified variants. Twenty-four SNPs were associated (P < 5 × 10−5) with RFI, ADG or FI. The variant rs43555985 exhibited strongest association for RFI (P = 8.28E-06). An eQTL was identified between this variant and GFRA2 (P = 0.0038) where the allele negatively correlated with RFI was associated with increased GFRA2 expression in liver. GFRA2 influences basal metabolic rates, suggesting a mechanism by which genetic variation may contribute to RFI. This study identified SNPs that may be useful both for genomic selection of RFI and for understanding the biology of feed efficiency.
Dendritic cell maturation in the corneal epithelium with onset of type 2 diabetes is associated with tumor necrosis factor receptor superfamily member 9
Authors: Lagali Neil S. , Badian Reza A. , Liu Xu , Feldreich Tobias R. , Ärnlöv Johan , Utheim Tor Paaske , Dahlin Lars B. , Rolandsson Olov
Published: September 2018

Type 2 diabetes mellitus is characterized by a low-grade inflammation; however, mechanisms leading to this inflammation in specific tissues are not well understood. The eye can be affected by diabetes; thus, we hypothesized that inflammatory changes in the eye may parallel the inflammation that develops with diabetes. Here, we developed a non-invasive means to monitor the status of inflammatory dendritic cell (DC) subsets in the corneal epithelium as a potential biomarker for the onset of inflammation in type 2 diabetes. In an age-matched cohort of 81 individuals with normal and impaired glucose tolerance and type 2 diabetes, DCs were quantified from wide-area maps of the corneal epithelial sub-basal plexus, obtained using clinical in vivo confocal microscopy (IVCM). With the onset of diabetes, the proportion of mature, antigen-presenting DCs increased and became organized in clusters. Out of 92 plasma proteins analysed in the cohort, tumor necrosis factor receptor super family member 9 (TNFRSF9) was associated with the observed maturation of DCs from an immature to mature antigen-presenting phenotype. A low-grade ocular surface inflammation observed in this study, where resident immature dendritic cells are transformed into mature antigen-presenting cells in the corneal epithelium, is a process putatively associated with TNFRSF9 signalling and may occur early in the development of type 2 diabetes. IVCM enables this process to be monitored non-invasively in the eye.
High resolution 7T and 9.4T-MRI of human cerebral arterial casts enables accurate estimations of the cerebrovascular morphometry
Authors: Helthuis Jasper H. G. , van der Zwan Albert , van Doormaal Tristan P. C. , Bleys Ronald L. A. W. , Harteveld Anita A. , van der Toorn Annette , Brozici Mariana , Hendrikse Jeroen , Zwanenburg Jaco J. M.
Published: September 2018

Quantitative data on the morphology of the cerebral arterial tree could aid in modelling and understanding cerebrovascular diseases, but is scarce in the range between 200 micrometres and 1 mm diameter arteries. Traditional manual measurements are difficult and time consuming. 7T-MRI and 9.4T-MRI of human cerebral arterial plastic casts could proof feasible for acquiring detailed morphological data of the cerebral arterial tree in a time efficient method. One cast of the complete human cerebral arterial circulation embedded in gadolinium-containing gelatine gel was scanned at 7T-MRI (0.1 mm isotropic resolution). A small section of another cast was scanned at 9.4T-MRI (30 µm isotropic resolution). Subsequent 3D-reconstruction was performed using a semi-automatic approach. Validation of 7T-MRI was performed by comparing the radius calculated using MRI to manual measurements on the same cast. As manual measurement of the small section was not feasible, 9.4T-MRI was validated by scanning the small section both at 7T-MRI and 9.4T MRI and comparing the diameters of arterial segments. Linear regression slopes were 0.97 (R-squared 0.94) and 1.0 (R-squared 0.90) for 7T-MRI and 9.4T-MRI. This data shows that 7T-MRI and 9.4T-MRI and subsequent 3D reconstruction of plastic casts is feasible, and allows for characterization of human cerebral arterial tree morphology.
Novel role for receptor dimerization in post-translational processing and turnover of the GRα
Authors: Wilkinson Legh , Verhoog Nicolette , Louw Ann
Published: September 2018

Glucocorticoids (GCs), acting via the glucocorticoid receptor (GRα), remain the mainstay therapeutic choice for the treatment of inflammation. However, chronic GC use, aside from generating undesirable side-effects, results in GRα down-regulation, often coupled to a decrease in GC-responsiveness, which may culminate in acquired GC resistance. The current study presents evidence for a novel role of the dimerization state of the GRα in mediating GC-mediated GRα turnover. Through comparing the effects of dimerization promoting GCs on down-regulation of a transfected human wild type GRα (hGRwt) or a dimerization deficient GRα mutant (hGRdim), we established that a loss of receptor dimerization restricts GRα turnover, which was supported by the use of the dimerization abrogating Compound A (CpdA), in cells containing endogenous GRα. Moreover, we showed that the dimerization state of the GRα influenced the post-translational processing of the receptor, specifically hyper-phosphorylation at Ser404, which influenced the interaction of GRα with the E3 ligase, FBXW7α, thus hampering receptor turnover via the proteasome. Lastly, the restorative effects of CpdA on the GRα pool, in the presence of Dex, were demonstrated in a combinatorial treatment protocol. These results expand our understanding of factors that contribute to GC-resistance and may be exploited clinically.
Reversible Human Immunodeficiency Virus Type-1 Latency in Primary Human Monocyte-Derived Macrophages Induced by Sustained M1 Polarization
Authors: Graziano Francesca , Aimola Giulia , Forlani Greta , Turrini Filippo , Accolla Roberto S. , Vicenzi Elisa , Poli Guido
Published: September 2018

We have reported that short-term stimulation of primary human monocyte-derived macrophages (MDM) with interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α), i.e. M1 polarization, leads to a significant containment of virus replication. Here we show that M1-MDM restimulation with these cytokines 7 days after infection (M12MDM) promoted an increased restriction of HIV-1 replication characterized by very low levels of virus production near to undetectable levels. In comparison to control and M1-MDM that were not restimulated, M12MDM showed a stronger reduction of both total and integrated HIV DNA as well as of viral mRNA expression. M12MDM were characterized by an upregulated expression of restriction factors acting at the level of reverse transcription (RT), including apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A (APOBEC3A) and APOBEC3G, but not SAM domain and HD domain-containing protein 1 (SAMHD1). M12MDM also showed an increased expression of Class II Transactivator (CIITA) and Tripartite Motif22 (TRIM22), two negative regulators of proviral transcription, whereas expression and phosphorylation of transcriptional inducers of HIV-1, such as nuclear factor kB (NF-kB) and signal transducer and activator of transcription 1 (STAT1), were not impaired in these cells. The almost quiescent state of the infection in M12MDM was promptly reversed by coculture with mitogen-stimulated leukocytes or cell incubation with their filtered culture supernatant. M12MDM harbored replication-competent HIV-1 as virus spreading following cell stimulation was fully prevented by the RT inhibitor lamivudine/3TC. Selective reactivation of proviral expression in M12MDM, but not in control or in M1-MDM that were not restimulated, was confirmed in cells infected with single round Vesicular Stomatitis Virus-G-pseudotyped HIV-1. Thus, M12MDM represent anin vitromodel of reversible, almost quiescent HIV-1 infection of primary human macrophages that could be further exploited for “Cure” related investigations.
The modification and characterization of thermal-treated sericite by fluorosilicate
Authors: Liang Yu , Jiang Wei , Ding Hao , Wang Yongkui
Published: September 2018

In this article, the thermal-treated sericite was modified by both fluorosilicate and the combination of fluorosilicate and nitric acid in order to reduce its layer charge and gain cation exchange capabilities for the preparation of sericite/polymer nanocomposites. After several orthogonal experiments and single factor experiments, the optimal experimental conditions were set up and we found that the combination of nitric acid and fluorosilicate is much more effective than fluorosilicate alone. Chemical composition analysis showed Al3+ was dissolved out from sericite and the dissolving amount is 65 mg/g under optimal experimental conditions. Combining the NMR test, it is considered that the Si/Al ratio in the tetrasheet of the modified product increased from 3.48 to 10. The layer charge reduced and the CEC value increased after fluorosilicate modification, which means the modified sericite is a promising matrix for clay-polymer nanocomposites.
Speckle tracking-derived bi-atrial strain before and after eleven weeks of training in elite rowers
Authors: Sareban Mahdi , Winkert Kay , Sperlich Billy , Berger Marc M. , Niebauer Josef , Steinacker Jürgen M. , Treff Gunnar
Published: September 2018

The left (LA) and right (RA) atria undergo adaptive remodeling in response to hemodynamic stress not only induced by endurance exercise but also as part of several cardiovascular diseases thereby confounding differential diagnosis. Echocardiographic assessment of the atria with novel speckle tracking (STE)-derived variables broadens the diagnostic spectrum compared to conventional analyses and has the potential to differentiate physiologic from pathologic changes. The purpose of this study was to assess and categorize baseline values of bi-atrial structure and function in elite rowers according to recommended cutoffs, and to assess the cardiac changes occurring with endurance training. Therefore, fifteen elite rowers underwent 2D-echocardiographic analysis of established variables of cardiac structure and function as well as STE-derived variables of bi-atrial function. Measurements were performed at baseline and after eleven weeks of extensive training. 40% of athletes displayed mildly enlarged LA and 47% mildly enlarged RA at baseline, whereas no athlete fell below the lower reference values of LA and RA reservoir strain. Average power during a 2000 m ergometer rowing test (P2000 m) improved from 426 ± 39 W to 442 ± 34 W (p = 0.010) but there were no changes of echocardiographic variables following training. In elite rowers, longitudinal bi-atrial strain assessment indicates normal resting function of structurally enlarged atria and thereby may assist to differentiate between exercise-induced versus disease-associated structural cardiac changes in which function is commonly impaired.
Identification of a limb enhancer that is removed by pathogenic deletions downstream of the SHOX gene
Authors: Skuplik Isabella , Benito-Sanz Sara , Rosin Jessica M. , Bobick Brent E. , Heath Karen E. , Cobb John
Published: September 2018

Haploinsufficiency of the human SHOX gene causes Léri-Weill dyschondrosteosis (LWD), characterized by shortening of the middle segments of the limbs and Madelung deformity of the wrist. As many as 35% of LWD cases are caused by deletions of non-coding sequences downstream of SHOX that presumably remove an enhancer or enhancers necessary for SHOX expression in developing limbs. We searched for these active sequences using a transgenic mouse assay and identified a 563 basepair (bp) enhancer with specific activity in the limb regions where SHOX functions. This enhancer has previously escaped notice because of its poor evolutionary conservation, although it does contain 100 bp that are conserved in non-rodent mammals. A primary cell luciferase assay confirmed the enhancer activity of the conserved core sequence and demonstrated that putative HOX binding sites are required for its activity. This enhancer is removed in most non-coding deletions that cause LWD. However, we did not identify any likely pathogenic variants of the enhancer in a screen of 124 LWD individuals for whom no causative mutation had been found, suggesting that only larger deletions in the region commonly cause LWD. We hypothesize that loss of this enhancer contributes to the pathogenicity of deletions downstream of SHOX.
Enantiomeric Aβ peptides inhibit the fluid shear stress response of PIEZO1
Authors: Maneshi Mohammad M. , Ziegler Lynn , Sachs Frederick , Hua Susan Z. , Gottlieb Philip A.
Published: September 2018

Traumatic brain injury (TBI) elevates Abeta (Aβ) peptides in the brain and cerebral spinal fluid. Aβ peptides are amphipathic molecules that can modulate membrane mechanics. Because the mechanosensitive cation channel PIEZO1 is gated by membrane tension and curvature, it prompted us to test the effects of Aβ on PIEZO1. Using precision fluid shear stress as a stimulus, we found that Aβ monomers inhibit PIEZO1 at femtomolar to picomolar concentrations. The Aβ oligomers proved much less potent. The effect of Aβs on Piezo gating did not involve peptide-protein interactions since the D and L enantiomers had similar effects. Incubating a fluorescent derivative of Aβ and a fluorescently tagged PIEZO1, we showed that Aβ can colocalize with PIEZO1, suggesting that they both had an affinity for particular regions of the bilayer. To better understand the PIEZO1 inhibitory effects of Aβ, we examined their effect on wound healing. We observed that over-expression of PIEZO1 in HEK293 cells increased cell migration velocity ~10-fold, and both enantiomeric Aβ peptides and GsMTx4 independently inhibited migration, demonstrating involvement of PIEZO1 in cell motility. As part of the motility study we examined the correlation of PIEZO1 function with tension in the cytoskeleton using a genetically encoded fluorescent stress probe. Aβ peptides increased resting stress in F-actin, and is correlated with Aβ block of PIEZO1-mediated Ca2+ influx. Aβ inhibition of PIEZO1 in the absence of stereospecific peptide-protein interactions shows that Aβ peptides modulate both cell membrane and cytoskeletal mechanics to control PIEZO1-triggered Ca2+ influx.
Effectiveness of monovalent rotavirus vaccine in the Philippines
Authors: Lopez Anna Lena , Daag Jedas Veronica , Esparagoza Joel , Bonifacio Joseph , Fox Kimberley , Nyambat Batmunkh , Parashar Umesh D. , Ducusin Maria Joyce , Tate Jacqueline E.
Published: September 2018

Rotavirus (RV) is an important cause of diarrheal disease particularly in children aged under 5 years. Monovalent RV vaccine (RVV) was selectively introduced in 2012 in the Philippines and in July 2014 was introduced in the public health program of a province. Two RVV doses are recommended at 6 and 10 weeks of age. We conducted a test negative case-control evaluation to assess the effectiveness of RVV when given in a routine public health program in the Philippines. From September 2014 to August 2017, 967 children aged <5 years were hospitalized with diarrhea and of these, we enrolled 600 who were eligible to have received RVV and provided stool specimens for testing. Among children ≥8 months of age who were age-eligible to have received RVV, at least one dose of RVV had an adjusted vaccine effectiveness (VE) against RV hospitalization of 60% (95% confidence interval, CI: 24%, 79%), and against severe rotavirus diarrhea, VE was 64% (95% CI: 11%, 85%). These findings support the introduction of RVV into routine public health use in the Philippines. However, other factors such as costs, cost-effectiveness and operational issues must be considered prior to adoption of the vaccine into the countries’ public immunization program.