bluuebunny/crossref_metadata_2025_split huggingface dataset:
Light-controlled switching of the spin state of iron(III)
Authors: Shankar Sreejith , Peters Morten , Steinborn Kim , Krahwinkel Bahne , Sönnichsen Frank D. , Grote Dirk , Sander Wolfram , Lohmiller Thomas , Rüdiger Olaf , Herges Rainer 
Published: November 2018

AbstractControlled switching of the spin state of transition metal ions, particularly of FeII and FeIII, is a prerequisite to achieve selectivity, efficiency, and catalysis in a number of metalloenzymes. Here we report on an iron(III) porphyrin with a photochromic axial ligand which, upon irradiation with two different wavelengths reversibly switches its spin state between low-spin (S = 1/2) and high-spin (S = 5/2) in solution (DMSO-acetone, 2:598). The switching efficiency is 76% at room temperature. The system is neither oxygen nor water sensitive, and no fatigue was observed after more than 1000 switching cycles. Concomitant with the spin-flip is a change in redox potential by ~60 mV. Besides serving as a simple model for the first step of the cytochrome P450 catalytic cycle, the spin switch can be used to switch the spin-lattice relaxation time T1 of the water protons by a factor of 15.
5D operando tomographic diffraction imaging of a catalyst bed
Authors: Vamvakeros A. , Jacques S. D. M. , Di Michiel M. , Matras D. , Middelkoop V. , Ismagilov I. Z. , Matus E. V. , Kuznetsov V. V. , Drnec J. , Senecal P. , Beale A. M. 
Published: November 2018

AbstractWe report the results from the first 5D tomographic diffraction imaging experiment of a complex Ni–Pd/CeO2–ZrO2/Al2O3 catalyst used for methane reforming. This five-dimensional (three spatial, one scattering and one dimension to denote time/imposed state) approach enabled us to track the chemical evolution of many particles across the catalyst bed and relate these changes to the gas environment that the particles experience. Rietveld analysis of some 2 × 106 diffraction patterns allowed us to extract heterogeneities in the catalyst from the Å to the nm and to the μm scale (3D maps corresponding to unit cell lattice parameters, crystallite sizes and phase distribution maps respectively) under different chemical environments. We are able to capture the evolution of the Ni-containing species and gain a more complete insight into the multiple roles of the CeO2-ZrO2 promoters and the reasons behind the partial deactivation of the catalyst during partial oxidation of methane.
REX1 is the critical target of RNF12 in imprinted X chromosome inactivation in mice
Authors: Gontan Cristina , Mira-Bontenbal Hegias , Magaraki Aristea , Dupont Catherine , Barakat Tahsin Stefan , Rentmeester Eveline , Demmers Jeroen , Gribnau Joost 
Published: November 2018

AbstractIn mice, imprinted X chromosome inactivation (iXCI) of the paternal X in the pre-implantation embryo and extraembryonic tissues is followed by X reactivation in the inner cell mass (ICM) of the blastocyst to facilitate initiation of random XCI (rXCI) in all embryonic tissues. RNF12 is an E3 ubiquitin ligase that plays a key role in XCI. RNF12 targets pluripotency protein REX1 for degradation to initiate rXCI in embryonic stem cells (ESCs) and loss of the maternal copy of Rnf12 leads to embryonic lethality due to iXCI failure. Here, we show that loss of Rex1 rescues the rXCI phenotype observed in Rnf12−/− ESCs, and that REX1 is the prime target of RNF12 in ESCs. Genetic ablation of Rex1 in Rnf12−/− mice rescues the Rnf12−/− iXCI phenotype, and results in viable and fertile Rnf12−/−:Rex1−/− female mice displaying normal iXCI and rXCI. Our results show that REX1 is the critical target of RNF12 in XCI.
Quantitative metaproteomics of medieval dental calculus reveals individual oral health status
Authors: Jersie-Christensen Rosa R. , Lanigan Liam T. , Lyon David , Mackie Meaghan , Belstrøm Daniel , Kelstrup Christian D. , Fotakis Anna K. , Willerslev Eske , Lynnerup Niels , Jensen Lars J. , Cappellini Enrico , Olsen Jesper V. 
Published: November 2018

AbstractThe composition of ancient oral microbiomes has recently become accessible owing to advanced biomolecular methods such as metagenomics and metaproteomics, but the utility of metaproteomics for such analyses is less explored. Here, we use quantitative metaproteomics to characterize the dental calculus associated with the remains of 21 humans retrieved during the archeological excavation of the medieval (ca. 1100–1450 CE) cemetery of Tjærby, Denmark. We identify 3671 protein groups, covering 220 bacterial species and 81 genera across all medieval samples. The metaproteome profiles of bacterial and human proteins suggest two distinct groups of archeological remains corresponding to health-predisposed and oral disease-susceptible individuals, which is supported by comparison to the calculus metaproteomes of healthy living individuals. Notably, the groupings identified by metaproteomics are not apparent from the bioarchaeological analysis, illustrating that quantitative metaproteomics has the potential to provide additional levels of molecular information about the oral health status of individuals from archeological contexts.
High-throughput three-dimensional chemotactic assays reveal steepness-dependent complexity in neuronal sensation to molecular gradients
Authors: Xu Zhen , Fang Peilin , Xu Bingzhe , Lu Yufeng , Xiong Jinghui , Gao Feng , Wang Xin , Fan Jun , Shi Peng 
Published: November 2018

AbstractMany cellular programs of neural development are under combinatorial regulation by different chemoattractive or chemorepulsive factors. Here, we describe a microfluidic platform that utilizes well-controlled three-dimensional (3D) diffusion to generate molecular gradients of varied steepness in a large array of hydrogel cylinders, allowing high-throughput 3D chemotactic assays for mechanistic dissection of steepness-dependent neuronal chemotaxis. Using this platform, we examine neuronal sensitivity to the steepness of gradient composed of netrin-1, nerve growth factor, or semaphorin3A (Sema3A) proteins, and reveal dramatic diversity and complexity in the associated chemotactic regulation of neuronal development. Particularly for Sema3A, we find that serine/threonine kinase-11 and glycogen synthase kinase-3 signaling pathways are differentially involved in steepness-dependent chemotactic regulation of coordinated neurite repellence and neuronal migration. These results provide insights to the critical role of gradient steepness in neuronal chemotaxis, and also prove the technique as an expandable platform for studying other chemoresponsive cellular systems.
Microevolution of Neisseria lactamica during nasopharyngeal colonisation induced by controlled human infection
Authors: Pandey Anish , Cleary David W. , Laver Jay R. , Gorringe Andrew , Deasy Alice M. , Dale Adam P. , Morris Paul D. , Didelot Xavier , Maiden Martin C. J. , Read Robert C. 
Published: November 2018

AbstractNeisseria lactamica is a harmless coloniser of the infant respiratory tract, and has a mutually-excluding relationship with the pathogen Neisseria meningitidis. Here we report controlled human infection with genomically-defined N. lactamica and subsequent bacterial microevolution during 26 weeks of colonisation. We find that most mutations that occur during nasopharyngeal carriage are transient indels within repetitive tracts of putative phase-variable loci associated with host-microbe interactions (pgl and lgt) and iron acquisition (fetA promotor and hpuA). Recurrent polymorphisms occurred in genes associated with energy metabolism (nuoN, rssA) and the CRISPR-associated cas1. A gene encoding a large hypothetical protein was often mutated in 27% of the subjects. In volunteers who were naturally co-colonised with meningococci, recombination altered allelic identity in N. lactamica to resemble meningococcal alleles, including loci associated with metabolism, outer membrane proteins and immune response activators. Our results suggest that phase variable genes are often mutated during carriage-associated microevolution.
Vibrio cholerae motility exerts drag force to impede attack by the bacterial predator Bdellovibrio bacteriovorus
Authors: Duncan Miles C. , Forbes John C. , Nguyen Y , Shull Lauren M. , Gillette Rebecca K. , Lazinski David W. , Ali Afsar , Shanks Robert M. Q. , Kadouri Daniel E. , Camilli Andrew 
Published: November 2018

AbstractThe bacterial predator Bdellovibrio bacteriovorus is evolved to attack and kill other bacteria, including the human intestinal pathogen Vibrio cholerae. Although B. bacteriovorus exhibit a broad prey range, little is known about the genetic determinants of prey resistance and sensitivity. Here we perform a genetic screen on V. cholerae and identify five pathways contributing to predation susceptibility. We find that the essential virulence regulators ToxR/S increase susceptibility to predation, as mutants of these genes are more resistant to predation. We observe by flow cytometry that lipopolysaccharide is a critical defense, as mutants lacking O-antigen are rapidly attacked by predatory B. bacteriovorus. Using polymer solutions to alter media viscosity, we find that when B. bacteriovorus attacks motile V. cholerae, increased drag forces slow its ability to prey. These results provide insights into key prey resistance mechanisms, and may be useful in the application of B. bacteriovorus in treating infections.
Near-infrared STED nanoscopy with an engineered bacterial phytochrome
Authors: Kamper Maria , Ta Haisen , Jensen Nickels A. , Hell Stefan W. , Jakobs Stefan 
Published: November 2018

AbstractThe near infrared (NIR) optical window between the cutoff for hemoglobin absorption at 650 nm and the onset of increased water absorption at 900 nm is an attractive, yet largely unexplored, spectral regime for diffraction-unlimited super-resolution fluorescence microscopy (nanoscopy). We developed the NIR fluorescent protein SNIFP, a bright and photostable bacteriophytochrome, and demonstrate its use as a fusion tag in live-cell microscopy and STED nanoscopy. We further demonstrate dual color red-confocal/NIR-STED imaging by co-expressing SNIFP with a conventional red fluorescent protein.
Structural insights into the function of type VI secretion system TssA subunits
Authors: Dix Samuel R. , Owen Hayley J. , Sun Ruyue , Ahmad Asma , Shastri Sravanthi , Spiewak Helena L. , Mosby Daniel J. , Harris Matthew J. , Batters Sarah L. , Brooker Thomas A. , Tzokov Svetomir B. , Sedelnikova Svetlana E. , Baker Patrick J. , Bullough Per A. , Rice David W. , Thomas Mark S. 
Published: November 2018

AbstractThe type VI secretion system (T6SS) is a multi-protein complex that injects bacterial effector proteins into target cells. It is composed of a cell membrane complex anchored to a contractile bacteriophage tail-like apparatus consisting of a sharpened tube that is ejected by the contraction of a sheath against a baseplate. We present structural and biochemical studies on TssA subunits from two different T6SSs that reveal radically different quaternary structures in comparison to the dodecameric E. coli TssA that arise from differences in their C-terminal sequences. Despite this, the different TssAs retain equivalent interactions with other components of the complex and position their highly conserved N-terminal ImpA_N domain at the same radius from the centre of the sheath as a result of their distinct domain architectures, which includes additional spacer domains and highly mobile interdomain linkers. Together, these variations allow these distinct TssAs to perform a similar function in the complex.
Increasing compound events of extreme hot and dry days during growing seasons of wheat and maize in China
Authors: Lu You , Hu Hongchang , Li Chao , Tian Fuqiang 
Published: November 2018

AbstractCompound events of climate extremes such as extremely high temperature and low precipitation during crop growing seasons can greatly affect agricultural production and food security. No study has investigated how Compound Extreme Hot and Dry days (CEHD days) during crop-growing seasons have changed or will change in response to climate warming. Based on observations, we find upward trends in CEHD days during wheat and maize growing seasons in China in the historical period 1980–2015. These trends are remarkably different during wheat and maize growing seasons, pointing to the need for targeted analysis focusing on crop-specific growing seasons. Projections of future temperature and precipitation from the Coordinated Regional Climate Downscaling Experiment show that upward trends will continue into future. On average over China, the frequencies of CEHD days during wheat and maize growing seasons are projected to increase respectively by 168% and 162% in 2036–2050 relatively to 1980–2015 under the RCP8.5 emissions scenario. The projected increases may have serious implications for China’s food production, adding to the need for resilience planning to limit the impacts of growing-season CEHD days.
Coherent Tabletop EUV Ptychography of Nanopatterns
Authors: Truong Nguyen Xuan , Safaei Reza , Cardin Vincent , Lewis Scott M. , Zhong Xiang Li , Légaré François , Denecke Melissa A. 
Published: November 2018

AbstractCoherent diffraction imaging (CDI) or lensless X-ray microscopy has become of great interest for high spatial resolution imaging of, e.g., nanostructures and biological specimens. There is no optics required in between an object and a detector, because the object can be fully recovered from its far-field diffraction pattern with an iterative phase retrieval algorithm. Hence, in principle, a sub-wavelength spatial resolution could be achieved in a high-numerical aperture configuration. With the advances of ultrafast laser technology, high photon flux tabletop Extreme Ultraviolet (EUV) sources based on the high-order harmonic generation (HHG) have become available to small-scale laboratories. In this study, we report on a newly established high photon flux and highly monochromatic 30 nm HHG beamline. Furthermore, we applied ptychography, a scanning CDI version, to probe a nearly periodic nanopattern with the tabletop EUV source. A wide-field view of about 15 × 15 μm was probed with a 2.5 μm−diameter illumination beam at 30 nm. From a set of hundreds of far-field diffraction patterns recorded for different adjacent positions of the object, both the object and the illumination beams were successfully reconstructed with the extended ptychographical iterative engine. By investigating the phase retrieval transfer function, a diffraction-limited resolution of reconstruction of about 32 nm is obtained.
Imaging the distribution of skin lipids and topically applied compounds in human skin using mass spectrometry
Authors: Sjövall Peter , Skedung Lisa , Gregoire Sébastien , Biganska Olga , Clément Franck , Luengo Gustavo S. 
Published: November 2018

AbstractThe barrier functions of skin against water loss, microbial invasion and penetration of xenobiotics rely, in part, on the spatial distribution of the biomolecular constituents in the skin structure, particularly its horny layer (stratum corneum). However, all skin layers are important to describe normal and dysfunctional skin conditions, and to develop adapted therapies or skin care products. In this work, time-of-flight secondary ion mass spectrometry (ToF-SIMS) combined with scanning electron microscopy (SEM) was used to image the spatial distribution of a variety of molecular species, from stratum corneum down to dermis, in cross-section samples of human abdominal skin. The results demonstrate the expected localization of ceramide and saturated long-chain fatty acids in stratum corneum (SC) and cholesterol sulfate in the upper part of the viable epidermis. The localization of exogenous compounds is demonstrated by the detection and imaging of carvacrol (a constituent of oregano or thyme essential oil) and ceramide, after topical application onto ex vivo human skin. Carvacrol showed pronounced accumulation to triglyceride-containing structures in the deeper parts of dermis. In contrast, the exogenous ceramide was found to be localized in SC. Furthermore, the complementary character of this approach with classical ex vivo skin absorption analysis methods is demonstrated.
Intrinsic disorder in the regulatory N-terminal domain of diacylglycerol acyltransferase 1 from Brassica napus
Authors: Panigrahi Rashmi , Matsui Tsutomu , Song Andrew H. , Caldo Kristian Mark P. , Young Howard S. , Weselake Randall J. , Lemieux M. Joanne 
Published: November 2018

AbstractProteins with multifunctional regulatory domains often demonstrate structural plasticity or protein disorder, allowing the binding of multiple regulatory factors and post-translational modifications. While the importance of protein disorder is clear, it also poses a challenge for in vitro characterization. Here, we report protein intrinsic disorder in a plant molecular system, which despite its prevalence is less studied. We present a detailed biophysical characterization of the entire cytoplasmic N-terminal domain of Brassica napus diacylglycerol acyltransferase, (DGAT1), which includes an inhibitory module and allosteric binding sites. Our results demonstrate that the monomeric N-terminal domain can be stabilized for biophysical characterization and is largely intrinsically disordered in solution. This domain interacts with allosteric modulators of DGAT1, CoA and oleoyl-CoA, at micromolar concentrations. While solution scattering studies indicate conformational heterogeneity in the N-terminal domain of DGAT1, there is a small gain of secondary structure induced by ligand binding.
An Algorithm for Enhancing the Image Contrast of Electron Tomography
Authors: Wu Hao , Zhai Xiaobo , Lei Dongsheng , Liu Jianfang , Yu Yadong , Bie Rongfang , Ren Gang 
Published: November 2018

AbstractThree-dimensional (3D) reconstruction of a single protein molecule is essential for understanding the relationship between the structural dynamics and functions of the protein. Electron tomography (ET) provides a tool for imaging an individual particle of protein from a series of tilted angles. Individual-particle electron tomography (IPET) provides an approach for reconstructing a 3D density map from a single targeted protein particle (without averaging from different particles of this type of protein), in which the target particle was imaged from a series of tilting angles. However, owing to radiation damage limitations, low-dose images (high noise, and low image contrast) are often challenging to be aligned for 3D reconstruction at intermediate resolution (1–3 nm). Here, we propose a computational method to enhance the image contrast, without increasing any experimental dose, for IPET 3D reconstruction. Using an edge-preserving smoothing-based multi-scale image decomposition algorithm, this method can detect the object against a high-noise background and enhance the object image contrast without increasing the noise level or significantly decreasing the image resolution. The method was validated by using both negative staining (NS) ET and cryo-ET images. The successful 3D reconstruction of a small molecule (<100 kDa) indicated that this method can be used as a supporting tool to current ET 3D reconstruction methods for studying protein dynamics via structure determination from each individual particle of the same type of protein.
NSAIDs-hypersensitivity often induces a blended reaction pattern involving multiple organs
Authors: Doña Inmaculada , Barrionuevo Esther , Salas María , Laguna José Julio , Agúndez José , García-Martín Elena , Bogas Gádor , Perkins James Richard , Cornejo-García José Antonio , Torres María José 
Published: November 2018

AbstractNon-steroidal anti-inflammatory drugs (NSAIDs)-induced hypersensitivity reactions are classified by the European Network on Drug Allergy (ENDA) as either cross-reactive or selective. The former is the most frequent type and includes patients with exclusively respiratory symptoms (NSAIDs-exacerbated respiratory disease, NERD) or exclusively cutaneous symptoms: NSAIDs-induced urticaria/angioedema (NIUA); and NSAIDs-exacerbated cutaneous disease (NECD). However, although not reflected in the current classification scheme (ENDA), in clinical practice a combination of both skin and respiratory symptoms or even other organs such as gastrointestinal tract symptoms (mixed or blended reactions) is frequently observed. This entity has not been sufficiently characterised. Our aim was to clinically characterize blended reactions to NSAIDs, comparing their clinical features with NERD and NIUA. We evaluated patients with symptoms suggestive of hypersensitivity to NSAIDs who attended the Allergy Unit of the Regional University Hospital of Malaga (Malaga, Spain) between 2008 and 2015. We included 880 patients confirmed as cross-reactive based on clinical history, positive nasal provocation test with lysine acetylsalicylate (NPT-LASA), and/or positive drug provocation test (DPT) with acetylsalicylic acid (ASA), who were classified as blended (261; 29.6%), NERD (108; 12.3%) or NIUA (511; 58.1%). We compared symptoms, drugs, underlying diseases and diagnostic methods within and between groups. Among blended patients the most common sub-group comprised those developing urticaria/angioedema plus rhinitis/asthma (n = 138), who had a higher percentage of underlying rhinitis (p < 0.0001) and asthma (p < 0.0001) than NIUA patients, showing similarities to NERD. These differences were not found in the sub-group of blended patients who developed such respiratory symptoms as glottis oedema; these were more similar to NIUA. The percentage of positive NPT-LASA was similar for blended (77%) and NERD groups (78.7%). We conclude that blended reactions are hypersensitivity reactions to NSAIDs affecting at least two organs. In addition to classical skin and respiratory involvement, in our population a number of patients also develop gastrointestinal symptoms. Given the high rate of positive responses to NPT-LASA in NERD as well as blended reactions, we suggest that all patients reporting respiratory symptoms, regardless of whether they have other associated symptoms, should be initially evaluated using NPT-LASA, which poses less risk than DPT.
Trends in Q fever serologic testing by immunofluorescence from four large reference laboratories in the United States, 2012–2016
Authors: Miller Halie K. , Binder Alison M. , Peterson Amy , Theel Elitza S. , Volpe Joseph M. , Couturier Marc Roger , Cherry Cara C. , Kersh Gilbert J. 
Published: November 2018

AbstractLaboratory testing for Q fever (Coxiella burnetii) is essential for a differential diagnosis, yet little is known about Q fever diagnostic testing practices in the United States. We retrospectively analyzed Q fever immunoglobulin G (IgG) indirect immunofluorescence assay (IFA) testing data between 1/1/2012–10/31/2016 from ARUP, LabCorp, Mayo Medical Laboratories, and Quest Diagnostics. Data included IgG phase I and phase II titers, patient age and sex, and state and date of specimen collection. On average, 12,821 specimens were tested for Q fever annually by the participating laboratories. Of 64,106 total specimens, 84.1% tested negative for C. burnetii-specific antibodies. Positive titers ranged from 16 to 262,144 against both phase I and phase II antigens. Submission of specimens peaked during the summer months, and more specimens were submitted from the West North Central division. Testing occurred more frequently in males (53%) and increased with age. In conclusion, few U.S. Q fever cases are reported, despite large volumes of diagnostic specimens tested. Review of commercial laboratory data revealed a lack of paired serology samples and patterns of serology titers that differ from case reporting diagnostic criteria.