bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural properties of a haemophore facilitate targeted elimination of the pathogen Porphyromonas gingivalis
Authors: Gao Jin-Long , Kwan Ann H. , Yammine Anthony , Zhou Xiaoyan , Trewhella Jill , Hugrass Barbara M. , Collins Daniel A. T. , Horne James , Ye Ping , Harty Derek , Nguyen Ky-Anh , Gell David A. , Hunter Neil
Published: October 2018

Porphyromonas gingivalisis a keystone bacterial pathogen of chronic periodontitis.P.gingivalisis unable to synthesise the porphyrin macrocycle and relies on exogenous porphyrin, including haem or haem biosynthesis intermediates from host sources. We show that under the iron-limited conditions prevailing in tissue environments,P.gingivalisexpresses a haemophore-like protein, HusA, to mediate the uptake of essential porphyrin and support pathogen survival within epithelial cells. The structure of HusA, together with titration studies, mutagenesis and in silico docking, show that haem binds in a hydrophobic groove on the α-helical structure without the typical iron coordination seen in other haemophores. This mode of interaction allows HusA to bind to a variety of abiotic and metal-free porphyrins with higher affinities than to haem. We exploit this unusual porphyrin-binding activity of HusA to target a prototypic deuteroporphyrin-metronidazole conjugate with restricted antimicrobial specificity in a Trojan horse strategy that effectively kills intracellularP. gingivalis.
Targeting of NLRP3 inflammasome with gene editing for the amelioration of inflammatory diseases
Authors: Xu Congfei , Lu Zidong , Luo Yingli , Liu Yang , Cao Zhiting , Shen Song , Li Hongjun , Liu Jing , Chen Kaige , Chen Zhiyao , Yang Xianzhu , Gu Zhen , Wang Jun
Published: October 2018

The NLRP3 inflammasome is a well-studied target for the treatment of multiple inflammatory diseases, but how to promote the current therapeutics remains a large challenge. CRISPR/Cas9, as a gene editing tool, allows for direct ablation of NLRP3 at the genomic level. In this study, we screen an optimized cationic lipid-assisted nanoparticle (CLAN) to deliver Cas9 mRNA (mCas9) and guide RNA (gRNA) into macrophages. By using CLAN encapsulating mCas9 and gRNA-targeting NLRP3 (gNLRP3) (CLANmCas9/gNLRP3), we disrupt NLRP3 of macrophages, inhibiting the activation of the NLRP3 inflammasome in response to diverse stimuli. After intravenous injection, CLANmCas9/gNLRP3 mitigates acute inflammation of LPS-induced septic shock and monosodium urate crystal (MSU)-induced peritonitis. In addition, CLANmCas9/gNLRP3 treatment improves insulin sensitivity and reduces adipose inflammation of high-fat-diet (HFD)-induced type 2 diabetes (T2D). Thus, our study provides a promising strategy for treating NLRP3-dependent inflammatory diseases and provides a carrier for delivering CRISPR/Cas9 into macrophages.
Bright room temperature single photon source at telecom range in cubic silicon carbide
Authors: Wang Junfeng , Zhou Yu , Wang Ziyu , Rasmita Abdullah , Yang Jianqun , Li Xingji , von Bardeleben Hans Jürgen , Gao Weibo
Published: October 2018

Single-photon emitters (SPEs) play an important role in a number of quantum information tasks such as quantum key distributions. In these protocols, telecom wavelength photons are desired due to their low transmission loss in optical fibers. In this paper, we present a study of bright single-photon emitters in cubic silicon carbide (3C-SiC) emitting in the telecom range. We find that these emitters are photostable and bright at room temperature with a count rate of ~ MHz. Altogether with the fact that SiC is a growth and fabrication-friendly material, our result may be relevant for future applications in quantum communication technology.
Publisher Correction: Necroptosis mediates myofibre death in dystrophin-deficient mice
Authors: Morgan Jennifer E. , Prola Alexandre , Mariot Virginie , Pini Veronica , Meng Jinhong , Hourde Christophe , Dumonceaux Julie , Conti Francesco , Relaix Frederic , Authier Francois-Jerôme , Tiret Laurent , Muntoni Francesco , Bencze Maximilien
Published: October 2018

The original version of this article contained an error in Fig. 3. In panel c, the labels ‘mdx’ and ‘mdx Ripk3-/-‘ were inadvertently inverted. This has now been corrected in the PDF and HTML versions of the Article.
Publisher Correction: Critical Southern Ocean climate model biases traced to atmospheric model cloud errors
Authors: Hyder Patrick , Edwards John M. , Allan Richard P. , Hewitt Helene T. , Bracegirdle Thomas J. , Gregory Jonathan M. , Wood Richard A. , Meijers Andrew J. S. , Mulcahy Jane , Field Paul , Furtado Kalli , Bodas-Salcedo Alejandro , Williams Keith D. , Copsey Dan , Josey Simon A. , Liu Chunlei , Roberts Chris D. , Sanchez Claudio , Ridley Jeff , Thorpe Livia , Hardiman Steven C. , Mayer Michael , Berry David I. , Belcher Stephen E.
Published: October 2018

'In the original HTML version of this Article, ref.12 was incorrectly cited in the first sentence of the first paragraph of the Introduction. The correct citation is ref. 2. This has now been corrected in the HTML version of the Article; the PDF version was correct at the time of publication.’
Author Correction: Multilayer networks reveal the spatial structure of seed-dispersal interactions across the Great Rift landscapes
Authors: Timóteo Sérgio , Correia Marta , Rodríguez-Echeverría Susana , Freitas Helena , Heleno Ruben
Published: October 2018

The original version of this Article contained Figshare links in the Code availability statement that were not functional. The correct Figshare links to MATLAB scripts and R code used in this study are https://doi.org/10.6084/m9.figshare.4955651 and https://doi.org/10.6084/m9.figshare.4836383, respectively. These errors have now been corrected in both the PDF and HTML versions of the Article.
High Speed, High Density Intraoperative 3D Optical Topographical Imaging with Efficient Registration to MRI and CT for Craniospinal Surgical Navigation
Authors: Jakubovic Raphael , Guha Daipayan , Gupta Shaurya , Lu Michael , Jivraj Jamil , Standish Beau A. , Leung Michael K. , Mariampillai Adrian , Lee Kenneth , Siegler Peter , Skowron Patryk , Farooq Hamza , Nguyen Nhu , Alarcon Joseph , Deorajh Ryan , Ramjist Joel , Ford Michael , Howard Peter , Phan Nicolas , Costa Leo da , Heyn Chris , Tan Gamaliel , George Rajeesh , Cadotte David W. , Mainprize Todd , Yee Albert , Yang Victor X. D.
Published: October 2018

Intraoperative image-guided surgical navigation for craniospinal procedures has significantly improved accuracy by providing an avenue for the surgeon to visualize underlying internal structures corresponding to the exposed surface anatomy. Despite the obvious benefits of surgical navigation, surgeon adoption remains relatively low due to long setup and registration times, steep learning curves, and workflow disruptions. We introduce an experimental navigation system utilizing optical topographical imaging (OTI) to acquire the 3D surface anatomy of the surgical cavity, enabling visualization of internal structures relative to exposed surface anatomy from registered preoperative images. Our OTI approach includes near instantaneous and accurate optical measurement of >250,000 surface points, computed at >52,000 points-per-second for considerably faster patient registration than commercially available benchmark systems without compromising spatial accuracy. Our experience of 171 human craniospinal surgical procedures, demonstrated significant workflow improvement (41 s vs. 258 s and 794 s, p < 0.05) relative to benchmark navigation systems without compromising surgical accuracy. Our advancements provide the cornerstone for widespread adoption of image guidance technologies for faster and safer surgeries without intraoperative CT or MRI scans. This work represents a major workflow improvement for navigated craniospinal procedures with possible extension to other image-guided applications.
Pathological macromolecular crystallographic data affected by twinning, partial-disorder and exhibiting multiple lattices for testing of data processing and refinement tools
Authors: Campeotto Ivan , Lebedev Andrey , Schreurs Antoine M. M. , Kroon-Batenburg Loes M. J. , Lowe Edward , Phillips Simon E. V. , Murshudov Garib N. , Pearson Arwen R.
Published: October 2018

Twinning is a crystal growth anomaly, which has posed a challenge in macromolecular crystallography (MX) since the earliest days. Many approaches have been used to treat twinned data in order to extract structural information. However, in most cases it is usually simpler to rescreen for new crystallization conditions that yield an untwinned crystal form or, if possible, collect data from non-twinned parts of the crystal. Here, we report 11 structures of engineered variants of the E. coli enzyme N-acetyl-neuraminic lyase which, despite twinning and incommensurate modulation, have been successfully indexed, solved and deposited. These structures span a resolution range of 1.45–2.30 Å, which is unusually high for datasets presenting such lattice disorders in MX and therefore these data provide an excellent test set for improving and challenging MX data processing programs.
Cytometry meets next-generation sequencing – RNA-Seq of sorted subpopulations reveals regional replication and iron-triggered prophage induction in Corynebacterium glutamicum
Authors: Freiherr von Boeselager Raphael , Pfeifer Eugen , Frunzke Julia
Published: October 2018

Phenotypic diversification is key to microbial adaptation. Currently, advanced technological approaches offer insights into cell-to-cell variation of bacterial populations at a spatiotemporal resolution. However, the underlying molecular causes or consequences often remain obscure. In this study, we developed a workflow combining fluorescence-activated cell sorting and RNA-sequencing, thereby allowing transcriptomic analysis of 106 bacterial cells. As a proof of concept, the workflow was applied to study prophage induction in a subpopulation of Corynebacterium glutamicum. Remarkably, both the phage genes and flanking genomic regions of the CGP3 prophage revealed significantly increased coverage upon prophage induction – a phenomenon that to date has been obscured by bulk approaches. Genome sequencing of prophage-induced populations suggested regional replication at the CGP3 locus in C. glutamicum. Finally, the workflow was applied to unravel iron-triggered prophage induction in early exponential cultures. Here, an up-shift in iron levels resulted in a heterogeneous response of an SOS (PdivS) reporter. RNA-sequencing of the induced subpopulation confirmed induction of the SOS response triggering also activation of the CGP3 prophage. The fraction of CGP3-induced cells was enhanced in a mutant lacking the iron regulator DtxR suffering from enhanced iron uptake. Altogether, these findings demonstrate the potential of the established workflow to gain insights into the phenotypic dynamics of bacterial populations.
VOC breath profile in spontaneously breathing awake swine during Influenza A infection
Authors: Traxler Selina , Bischoff Ann-Christin , Saß Radost , Trefz Phillip , Gierschner Peter , Brock Beate , Schwaiger Theresa , Karte Claudia , Blohm Ulrike , Schröder Charlotte , Miekisch Wolfram , Schubert Jochen K.
Published: October 2018

Influenza is one of the most common causes of virus diseases worldwide. Virus detection requires determination of Influenza RNA in the upper respiratory tract. Efficient screening is not possible in this way. Analysis of volatile organic compounds (VOCs) in breath holds promise for non-invasive and fast monitoring of disease progression. Breath VOC profiles of 14 (3 controls and 11 infected animals) swine were repeatedly analyzed during a complete infection cycle of Influenza A under high safety conditions. Breath VOCs were pre-concentrated by means of needle trap micro-extraction and analysed by gas chromatography mass spectrometry before infection, during virus presence in the nasal cavity, and after recovery. Six VOCs could be related to disease progression: acetaldehyde, propanal, n-propyl acetate, methyl methacrylate, styrene and 1,1-dipropoxypropane. As early as on day four after inoculation, when animals were tested positive for Influenza A, differentiation between control and infected animals was possible. VOC based information on virus infection could enable early detection of Influenza A. As VOC analysis is completely non-invasive it has potential for large scale screening purposes. In a perspective, breath analysis may offer a novel tool for Influenza monitoring in human medicine, animal health control or border protection.
A genomic Neolithic time transect of hunter-farmer admixture in central Poland
Authors: Fernandes D. M. , Strapagiel D. , Borówka P. , Marciniak B. , Żądzińska E. , Sirak K. , Siska V. , Grygiel R. , Carlsson J. , Manica A. , Lorkiewicz W. , Pinhasi R.
Published: October 2018

Ancient DNA genome-wide analyses of Neolithic individuals from central and southern Europe indicate an overall population turnover pattern in which migrating farmers from Anatolia and the Near East largely replaced autochthonous Mesolithic hunter-gatherers. However, the genetic history of the Neolithic transition in areas lying north of the European Neolithic core region involved different levels of admixture with hunter-gatherers. Here we analyse genome-wide data of 17 individuals spanning from the Middle Neolithic to the Early Bronze Age (4300-1900 BCE) in order to assess the Neolithic transition in north-central Poland, and the local impacts of hunter-farmer contacts and Late Neolithic steppe migrations. We evaluate the influence of these on local populations and assess if and how they change through time, reporting evidence of recurrent hunter-farmer admixture over three millennia, and the co-existence of unadmixed hunter-gatherers as late as 4300 BCE. During the Late Neolithic we report the appearance of steppe ancestry, but on a lesser scale than previously described for other central European regions, with evidence of stronger affinities to hunter-gatherers than to steppe pastoralists. These results help understand the Neolithic palaeogenomics of another central European area, Kuyavia, and highlight the complexity of population interactions during those times.
Machine-learning based lipid mediator serum concentration patterns allow identification of multiple sclerosis patients with high accuracy
Authors: Lötsch Jörn , Schiffmann Susanne , Schmitz Katja , Brunkhorst Robert , Lerch Florian , Ferreiros Nerea , Wicker Sabine , Tegeder Irmgard , Geisslinger Gerd , Ultsch Alfred
Published: October 2018

Based on increasing evidence suggesting that MS pathology involves alterations in bioactive lipid metabolism, the present analysis was aimed at generating a complex serum lipid-biomarker. Using unsupervised machine-learning, implemented as emergent self-organizing maps of neuronal networks, swarm intelligence and Minimum Curvilinear Embedding, a cluster structure was found in the input data space comprising serum concentrations of d = 43 different lipid-markers of various classes. The structure coincided largely with the clinical diagnosis, indicating that the data provide a basis for the creation of a biomarker (classifier). This was subsequently assessed using supervised machine-learning, implemented as random forests and computed ABC analysis-based feature selection. Bayesian statistics-based biomarker creation was used to map the diagnostic classes of either MS patients (n = 102) or healthy subjects (n = 301). Eight lipid-markers passed the feature selection and comprised GluCerC16, LPA20:4, HETE15S, LacCerC24:1, C16Sphinganine, biopterin and the endocannabinoids PEA and OEA. A complex classifier or biomarker was developed that predicted MS at a sensitivity, specificity and accuracy of approximately 95% in training and test data sets, respectively. The present successful application of serum lipid marker concentrations to MS data is encouraging for further efforts to establish an MS biomarker based on serum lipidomics.
Evidence of a Causal Role for mid-Ventrolateral Prefrontal Cortex Based Functional Networks in Retrieving High-Fidelity Memory
Authors: Wais Peter E. , Montgomery Olivia , Stark Craig E. L. , Gazzaley Adam
Published: October 2018

Functional neuroimaging studies have implicated regions of both ventrolateral prefrontal cortex (VLPFC) and angular gyrus in processes associated with retrieving goal-relevant information, which increases the fidelity and richness of long-term memory (LTM). To further investigate the roles of these cortical regions as nodes in functional networks with memory regions of the medial temporal lobe (MTL), we used fMRI-guided, 1 Hz repetitive transcranial magnetic stimulation (rTMS) to perturb normal neuronal function. The aim was to test the causal roles of left mid-VLPFC and left angular gyrus (AG) in MTL-VLPFC-parietal networks that have been associated with high-fidelity memory retrieval. rTMS treatments were administered immediately before blocks in an old/new recognition test, which was based on a mnemonic similarity task requiring discrimination of previously studied pictures of common objects. Capability for mnemonic discrimination was evaluated after each of three conditions: placebo control (rTMS at somatosensory cortex), mid-VLPFC target (rTMS at left pars triangularis) and parietal target (rTMS at left AG). The results showed the effect of rTMS perturbation of mid-VLPFC diminished subsequent discrimination-based memory performance, relative to placebo control, and no significant effect of perturbation of AG. These findings show a causal role for functional networks with left mid-VLPFC in high-fidelity retrieval.
Temporal differentiation of bovine airway epithelial cells grown at an air-liquid interface
Authors: Cozens Daniel , Sutherland Erin , Marchesi Francesco , Taylor Geraldine , Berry Catherine C. , Davies Robert L.
Published: October 2018

There is an urgent need to develop improved, physiologically-relevant in vitro models of airway epithelia with which to better understand the pathological processes associated with infection, allergies and toxicological insults of the respiratory tract of both humans and domesticated animals. In the present study, we have characterised the proliferation and differentiation of primary bovine bronchial epithelial cells (BBECs) grown at an air-liquid interface (ALI) at three-day intervals over a period of 42 days from the introduction of the ALI. The differentiated BBEC model was highly representative of the ex vivo epithelium from which the epithelial cells were derived; a columnar, pseudostratified epithelium that was highly reflective of native airway epithelium was formed which comprised ciliated, goblet and basal cells. The hallmark defences of the respiratory tract, namely barrier function and mucociliary clearance, were present, thus demonstrating that the model is an excellent mimic of bovine respiratory epithelium. The epithelium was fully differentiated by day 21 post-ALI and, crucially, remained healthy and stable for a further 21 days. Thus, the differentiated BBEC model has a three-week window which will allow wide-ranging and long-term experiments to be performed in the fields of infection, toxicology or general airway physiology.
The quantum Zeno and anti-Zeno effects with non-selective projective measurements
Authors: Majeed Mehwish , Chaudhry Adam Zaman
Published: October 2018

In studies of the quantum Zeno and anti-Zeno effects, it is usual to consider rapid projective measurements with equal time intervals being performed on the system to check whether or not the system is in the initial state. These projective measurements are selective measurements in the sense that the measurement results are read out and only the case where all the measurement results correspond to the initial state is considered in the analysis of the effect of the measurements. In this paper, we extend such a treatment to consider the effect of repeated non-selective projective measurements – only the final measurement is required to correspond to the initial state, while we do not know the results of the intermediate measurements. We present a general formalism to derive the effective decay rate of the initial quantum state with such nonselective measurements. Importantly, we show that there is a difference between using non-selective projective measurements and the usual approach of considering only selective measurements only if we go beyond the weak system-environment coupling regime in models other than the usual population decay models. As such, we then apply our formalism to investigate the quantum Zeno and anti-Zeno effects for three exactly solvable system-environment models: a single two-level system undergoing dephasing, a single two-level system interacting with an environment of two-level systems and a large spin undergoing dephasing. Our results show that the quantum Zeno and anti-Zeno effects in the presence of non-selective projective measurements can differ very significantly as compared to the repeated selective measurement scenario.
Formation of massive iron deposits linked to explosive volcanic eruptions
Authors: Ovalle J. Tomás , La Cruz Nikita L. , Reich Martin , Barra Fernando , Simon Adam C. , Konecke Brian A. , Rodriguez-Mustafa María A. , Deditius Artur P. , Childress Tristan M. , Morata Diego
Published: October 2018

The genetic link between magmas and ore deposit formation is well documented by studies of fossil hydrothermal systems associated with magmatic intrusions at depth. However, the role of explosive volcanic processes as active agents of mineralization remains unexplored owing to the fact that metals and volatiles are released into the atmosphere during the eruption of arc volcanoes. Here, we draw on observations of the uniquely preserved El Laco iron deposit in the Central Andes to shed new light on the metallogenic role of explosive volcanism that operates on a global scale. The massive magnetite (Fe3O4) ore bodies at El Laco have surface structures remarkably similar to basaltic lava flows, stimulating controversy about their origin. A long-standing debate has endured because all proposed models were constructed based exclusively on samples collected from surface outcrops representing the uppermost and most altered portion of the deposit. We overcome this sampling bias by studying samples retrieved from several drill cores and surface outcrops. Our results reveal complex lithological, textural and geochemical variations characterized by magmatic-like features and, most notably, a systematic increase in titanium concentration of magnetite with depth that account for an evolving system transitioning from purely magmatic to magmatic-hydrothermal conditions. We conclude that El Laco, and similar deposits worldwide, formed by a synergistic combination of common magmatic processes enhanced during the evolution of caldera-related explosive volcanic systems.
Relationship between Ocular Deviation and Visual Function in Retinitis Pigmentosa
Authors: Miyata Manabu , Oishi Akio , Ogino Ken , Oishi Maho , Hasegawa Tomoko , Nagasaku Yuko , Ikeda Hanako Ohashi , Ohtsuki Hiroshi , Tsujikawa Akitaka
Published: October 2018

In retinitis pigmentosa (RP), peripheral visual-field loss starts in early stages, whereas central vision loss occurs in advanced stages. Sensory strabismus gradually occurs in RP. We investigated the relationship between ocular deviation and visual function and explored for sensory strabismus risk factors in 119 consecutive patients with RP at various stages. We assessed ocular deviation at far and near distances, that is the central visual field, using the mean deviation (MD) value and visual acuity (VA), and the residual binocular field area, using Goldmann perimetry (GP), in 33 patients. The horizontal ocular deviation at near distance was >10° in 30% patients and correlated with residual visual function. Although there was no effective cut-off value for central visual function, a cut-off residual GP area of 40 cm2 distinguished patients with a larger from those with a smaller horizontal ocular deviation at far distance (P = 0.04). Our findings suggest that visual function is negatively associated with ocular deviation in patients with RP and that the sensory strabismus risk is relatively high for patients with a binocular visual field <40 cm2. Thus, screening for ocular alignment may be necessary for patients with RP-associated severe vision loss as part of their comprehensive care.
Spatial congruence between multiple stressors in the Mediterranean Sea may reduce its resilience to climate impacts
Authors: Ramírez Francisco , Coll Marta , Navarro Joan , Bustamante Javier , Green Andy J.
Published: October 2018

Climate impacts on marine ecosystems may be exacerbated by other, more local stressors interacting synergistically, such as pollution and overexploitation of marine resources. The reduction of these human stressors has been proposed as an achievable way of retaining ecosystems within a “safe operating space” (SOS), where they remain resilient to ongoing climate change. However, the operability of an SOS requires a thorough understanding of the spatial distribution of these climate and human impacts. Using the Mediterranean Sea as a case study, we illustrate the spatial congruence between climate and human stressors impacting this iconic “miniature ocean” synergistically. We use long-term, spatially-explicit information on the distribution of multiple stressors to identify those highly impacted marine areas where human stressors should be prioritized for management if the resilience to climate impacts is to be maintained. Based on our spatial analysis, we exemplify how the management of an essential supporting service (seafood provision) and the conservation of a highly impacted Mediterranean sub-region (the Adriatic Sea) may benefit from the SOS framework.
Genome-wide methylation analysis identifies ELOVL5 as an epigenetic biomarker for the risk of type 2 diabetes mellitus
Authors: Hwang Joo-Yeon , Lee Hyo Jung , Go Min Jin , Jang Han Byul , Choi Nak-Hyun , Bae Jae Bum , Castillo-Fernandez Juan E. , Bell Jordana T. , Spector Tim D. , Lee Hye-Ja , Kim Bong-Jo
Published: October 2018

Genome-wide DNA methylation has been implicated in complex human diseases. Here, we identified epigenetic biomarkers for type 2 diabetes (T2D) underlying obesogenic environments. In a blood-based DNA methylation analysis of 11 monozygotic twins (MZTW) discordant for T2D, we discovered genetically independent candidate methylation sites. In a follow-up replication study (17 MZTW pairs) for external validation, we replicated the T2D-association at a novel CpG signal in the ELOVL fatty acid elongase 5 (ELOVL5) gene specific to T2D-discordant MZTW. For concordant DNA methylation signatures in tissues, we further confirmed that a CpG site (cg18681426) was associated with adipogenic differentiation between human preadipocytes and adipocytes isolated from the same biopsy sample. In addition, the ELOVL5 gene was significantly differentially expressed in adipose tissues from unrelated T2D patients and in human pancreatic islets. Our results demonstrate that blood-derived DNA methylation is associated with T2D risk as a proxy for cumulative epigenetic status in human adipose and pancreatic tissues. Moreover, ELOVL5 expression was increased in cellular and mouse models of induced obesity-related diabetes. These findings may provide new insights into epigenetic architecture by uncovering methylation-based biomarkers.
Dual Porosity Protein-based Scaffolds with Enhanced Cell Infiltration and Proliferation
Authors: Rasoulianboroujeni Morteza , Kiaie Nasim , Tabatabaei Fahimeh Sadat , Yadegari Amir , Fahimipour Farahnaz , Khoshroo Kimia , Tayebi Lobat
Published: October 2018

3D dual porosity protein-based scaffolds have been developed using the combination of foaming and freeze-drying. The suggested approach leads to the production of large, highly porous scaffolds with negligible shrinkage and deformation compared to the conventional freeze-drying method. Scanning electron microscopy, standard histological processing and mercury intrusion porosimetry confirmed the formation of a dual network in the form of big primary pores (243 ± 14 µm) embracing smaller secondary pores (42 ± 3 µm) opened onto their surface, resembling a vascular network. High interconnectivity of the pores, confirmed by micro-CT, is shown to improve diffusion kinetics and support a relatively uniform distribution of isolated human dental pulp stem cells within the scaffold compared to conventional scaffolds. Dual network scaffolds indicate more than three times as high cell proliferation capability as conventional scaffolds in 14 days.
Bulk band inversion and surface Dirac cones in LaSb and LaBi: Prediction of a new topological heterostructure
Authors: Dey Urmimala , Chakraborty Monodeep , Taraphder A. , Tewari Sumanta
Published: October 2018

We perform ab initio investigations of the bulk and surface band structures of LaSb and LaBi and resolve the existing disagreements about the topological property of LaSb, considering LaBi as a reference. We examine the bulk band structure for band inversion, along with the stability of surface Dirac cones (if any) to time-reversal-preserving perturbations, as a strong diagnostic test for determining the topological character of LaSb, LaBi and LaSb-LaBi multilayer. A detailed ab initio investigation of a multilayer consisting of alternating unit cells of LaSb and LaBi shows the presence of band inversion in the bulk and a massless Dirac cone on the (001) surface, which remains stable under the influence of time-reversal-preserving perturbations, thus confirming the topologically non-trivial nature of the multilayer in which the electronic properties can be tailored as per requirement. A detailed $${{\mathbb{Z}}}_{2}$$

Z

2

invariant calculation is performed to arrive at a holistic conclusion.
Variability of crossing phase in older people with Parkinson’s disease is dependent of obstacle height
Authors: Simieli Lucas , Barbieri Fabio Augusto , Orcioli-Silva Diego , Lirani-Silva Ellen , Beretta Victor Spiandor , Santos Paulo Cezar Rocha dos , Gobbi Lilian Teresa Bucken
Published: October 2018

Our aim was investigating variability in spatiotemporal parameters and kinetics of obstacle avoidance steps of different height obstacles in people with Parkinson’s disease (PD) and healthy older people. Twenty-eight participants have included (15 PD – stage disease: 2.1 ± 0.4 pts) and 13 healthy older people (control group). Each subject performed 10 trials of the following tasks: low obstacle, intermediate obstacle and high obstacle. The presentation order was randomized by block for each condition and participant. The spatiotemporal parameters was collected by GAITRite. An optoelectronic system (Optotrak Northern Digital Inc.) with 100 Hz of frequency was used to collect obstacle parameters. The kinect parameters (propulsion impulse and braking impulse) were acquire through two force plates (AccuGait), with a frequency of acquisition 200 Hz. Intersteps variability was calculated throughout mean values, standard deviation and coefficient of variation of two obstacle avoidance steps for each trial. PD group presented greater variability than control group on vertical and horizontal distances to the obstacle. Obstacle height did not change kinect’s parameters for both groups. The combination of task complexity (obstacle height) and disease impairments (gait alteration, loss of balance, etc) contributing for greater variability of Parkinson’s group. Besides, low obstacle and high obstacle seem to exacerbate variability of distance between obstacle and foot.
Assembling the genome of the African wild rice Oryza longistaminata by exploiting synteny in closely related Oryza species
Authors: Reuscher Stefan , Furuta Tomoyuki , Bessho-Uehara Kanako , Cosi Michele , Jena Kshirod K. , Toyoda Atsushi , Fujiyama Asao , Kurata Nori , Ashikari Motoyuki
Published: October 2018

The African wild rice species Oryza longistaminata has several beneficial traits compared to cultivated rice species, such as resistance to biotic stresses, clonal propagation via rhizomes, and increased biomass production. To facilitate breeding efforts and functional genomics studies, we de-novo assembled a high-quality, haploid-phased genome. Here, we present our assembly, with a total length of 351 Mb, of which 92.2% was anchored onto 12 chromosomes. We detected 34,389 genes and 38.1% of the genome consisted of repetitive content. We validated our assembly by a comparative linkage analysis and by examining well-characterized gene families. This genome assembly will be a useful resource to exploit beneficial alleles found in O. longistaminata. Our results also show that it is possible to generate a high-quality, functionally complete rice genome assembly from moderate SMRT read coverage by exploiting synteny in a closely related Oryza species.
Dioxygen Binding and Activation Mediated by Transition Metal Porphyrinoid Complexes
Authors: Zaragoza Jan Paulo T. , Goldberg David P.
Published: October 2018

Heme-containing proteins play an essential part in the physiological transport of dioxygen, and in the oxidative metabolism of both endogenous and exogenous substrates. These latter processes occur through a series of highly reactive heme–oxygen intermediates. The development of synthetic analogues of these proteins and metal–oxygen intermediates has helped to elucidate the molecular mechanisms of these proteins and to establish the fundamental criteria for metal binding and activation of O2. This chapter outlines the basic chemical principles that govern the binding and activation of dioxygen by metalloporphyrinoid centers. An overview of the structures and mechanisms of heme mono- and dioxygenases is provided, with an emphasis on the factors that stabilize or activate the heme/O2 interactions. Focus is given to iron and manganese porphyrinoid complexes, which include porphyrins, corroles, corrolazines, porphyrazines, and phthalocyanines. Recent examples of metal/O2 species are discussed, together with catalytic, O2-dependent oxidations of different substrates mediated by Mn/Fe porphyrinoid complexes.
Investigating Heme Enzymes with Expanded Genetic Codes
Authors: Hu Cheng , Yu Yang , Wang Jiangyun
Published: October 2018

Heme enzymes have attracted lots of attention due to their significance in physiology and potential application in synthetic chemistry. Genetic code expansion has become a powerful technique in protein engineering in recent years. It also has wide applications in heme protein studies. Many site-specific incorporated probes have been reported for heme protein structural studies, including nuclear magnetic resonance (NMR) probes, spin probes and infrared probes. Together with newly developed spectroscopic methods, structure information which cannot be gained using traditional methods has been revealed. Meanwhile, genetically encoded unnatural amino acids with novel chemical properties have brought about new opportunities in heme enzyme design and optimization, such as the precise design of the coordination environment, and tuning of the steric and redox properties of the protein scaffold. Site-specific immobilization based on genetically encoded “click” probes has shown potential application in enzyme electrocatalysis, which is crucial for the large-scale synthetic application of heme enzymes. With continuous progress in both genetic code expansion methods and heme enzyme studies, inspiring achievements are expected in the future.
What Drives the Rate-determining Step for Oxygen Atom Transfer by Heme Compound I?
Authors: de Visser Sam P.
Published: October 2018

Understanding the catalytic properties of reactive species is an important concept in chemical catalysis, and in particular, computational modelling has been shown to provide useful insights into reaction mechanisms that lead to products and by-products. In recent years, several approaches have been reported that tried to generalize the reactivity trends of substrate oxidation reactions, for instance, to rationalize the oxidative patterns of the active species of heme peroxidases and the cytochrome P450s. Particularly useful are valence bond curve crossing diagrams that explain the mechanisms by dissecting the rate-determining barrier height for the reaction into components related to bond formation and bond breaking (or orbital formation and orbital breaking) processes and electron transfer steps. Very recently, we developed a novel two-parabola valence bond model for reactivity trends that enables one to predict enthalpies of activation, and consequently rate constants, from empirical values. Details of the methodology are described and examples are given on how to apply the two-parabola valence bond model in catalysis. Several case studies are given on heme Compound I reactivity that predict experimental reaction rates ab initio, but also predict regio- and chemoselectivities. It is worth noting that trends in hydrogen atom abstraction reactions by a cytochrome P450 model as calculated using density functional theory can be perfectly reproduced with the new model with a slope of unity and less than 1 kcal mol−1 systematic error.
Cytochrome P450 Decarboxylases
Authors: Makris Thomas M.
Published: October 2018

The cytochrome P450 OleT catalyzes the H2O2-dependent conversion of fatty acids to 1-olefins and carbon dioxide. The atypical nature of this reaction, coupled with its potential for sustainable fuel synthesis, has generated a great deal of interest since its discovery. The intriguing molecular mechanism of OleT and its potential for fungible fuel production is reviewed, revealing an interesting deviation from the activated oxygen-rebound chemistry that is common to most P450 monooxygenases.
Biological Heme Degradation
Authors: Ikeda-Saito Masao
Published: October 2018

Biological heme degradation is a physiologically important process not only for mammals, but also for plants and pathogenic bacteria. Heme catabolism is essential for mammalian iron homeostasis, for light-sensing billin biosynthesis in cyanobacteria and plants, and iron acquisition from host hemin in some pathogenic bacteria. Heme oxygenase, HO, which catalyzes the conversion of hemin to free iron, carbon monoxide, and biliverdin, has been considered as a sole player in biological heme degradation. HO attains this task by three successive monooxygenation reactions through meso-hydroxyheme and verdoheme intermediates, utilizing three oxygen molecules and seven electrons. The HO catalytic mechanism is now mostly understood. Recent discovery of new heme degrading enzymes, IsdG and IsdI, of Staphylococcus aureus and MhuD of Mycobacterium tuberculosis, extends the spectrum of heme degradation. MhuD degrades hemin to free iron and mycobilin where α-meso carbon retains a formyl group through sequential mono- and dioxygenase reactions. The IsdG reaction forms staphylobilin isomers with the release of iron and formaldehyde. This chapter will review the catalytic mechanisms of HO and IsdG-type enzymes.
Structure, Function and Regulation of Human Heme-based Dioxygenases
Authors: Lewis-Ballester Ariel , Pham Khoa N. , Liao Mingxiang , Correia Maria Almira , Yeh Syun-Ru
Published: October 2018

Dioxygenases belong to one of the three major classes of heme-based enzymes that utilize atmospheric O2 as a substrate. Oxidases, such as cytochrome c oxidase, reduce O2 to two water molecules by utilizing four electrons and four protons, and harness the redox energy to pump four protons across the protein matrix. Monooxygenases, such as P450, convert one atom of dioxygen to a water by consuming two electrons and two protons, and exploit the redox energy to insert the other oxygen atom into an organic substrate. Dioxygenases, including tryptophan dioxygenase (TDO) and indoleamine 2,3-dioxygenase 1 (IDO1), are unique, and least understood, as they are capable of inserting both atoms of O2 into Trp without using any electrons and protons. In Part A of this chapter, we review the structure and function relationships of human TDO and IDO1 and compare them with those of bacterial TDOs and two dioxygenase analogs, PrnB and MarE. In Part B we outline the mechanisms by which the TDO and IDO1 functions are regulated in vivo by a variety of effectors under various (patho)physiological conditions.
Conformational Changes in Cytochrome P450cam and the Effector Role of Putidaredoxin
Authors: Goodin David B. , Chuo Shih-Wei , Liou Shu-Hao
Published: October 2018

The cytochromes P450 form an enormous family of over 20 000 enzyme variants found in all branches of life. They catalyze the O2 dependent monooxygenation of a wide range of substrates in reactions important to drug metabolism, biosynthesis and energy utilization. Understanding how they function is important for biomedical science and requires a full description of their notorious propensity for specificity and promiscuity. The bacterial P450cam is an unusual example, having the most well characterized chemical mechanism of all of the forms. It also undergoes an increasingly well characterized structural change upon substrate binding, which may be similar to to that displayed by some, but not all forms of P450. Finally, P450cam is one of the rare forms that have a strict requirement for a particular electron donor, putidaredoxin (pdx). Pdx provides the required electrons for enzyme turnover, but it also induces specific changes in the enzyme to allow enzyme turnover, long known as its effector role. This review summarizes recent crystallographic and double electron–electron resonance studies that have revealed the effects of substrate and pdx binding on the structure of P450cam. We describe an emerging idea for how pdx exerts its effector function by inducing a conformational change in the enzyme. This change then propagates to the active site to enable cleavage of the ferric–hydroperoxy bond during catalysis, and appears to provide a very elegant approach for P450cam to attain both high efficiency and protection from oxidative damage.
Oxygen Reduction and Proton Translocation by Respiratory Cytochrome c Oxidase
Authors: Wikström Mårten , Sharma Vivek
Published: October 2018

Cell respiration is mainly catalysed by the so-called heme–copper oxygen reductases, which are characterised by a binuclear active site containing an oxygen-binding heme group and a nearby copper ion. The copper ion is ligated by three histidine residues, one of which is covalently bonded to a tyrosine residue and takes active part in the reduction of O2 to water. In addition, a low-spin heme is located adjacent to the oxygen-binding heme serving as the immediate electron donor to the binuclear site. Binding of O2 is followed by a “concerted” four-electron reduction confined within the binuclear site, leaving the site in a highly oxidised configuration, akin to the classical Compound I of the peroxidases and catalase. The catalytic cycle is then completed by sequential additions of four electrons to the binuclear centre, one at a time, to end up in the initial reduced state that binds the next O2. These four electron transfers are intimately coupled to proton translocation across the mitochondrial (or bacterial) membrane, which gives the function of the heme–copper oxygen reductases an additional intriguing dimension.
Analysis of soluble or titanium dioxide derived titanium levels in human whole blood: consensus from an inter-laboratory comparison
Authors: Koller D. , Bramhall P. , Devoy J. , Goenaga-Infante H. , Harrington C. F. , Leese E. , Morton J. , Nuñez S. , Rogers J. , Sampson B. , Powell J. J.
Published: October 2018

Exposure to titanium (Ti),viathe ingestion of pigment grade Ti dioxide (TiO2), is commonplace for westernised populations.
Fluid-permeable enzymatic lactate sensors for micro-volume specimen
Authors: Kai Hiroyuki , Kato Yuto , Toyosato Ryoma , Nishizawa Matsuhiko
Published: October 2018

A fluid-permeable enzymatic electrode can measure lactate in a small volume of artificial perspiration.
Lectin inspired polymers based on the dipeptide Ser-Asp for glycopeptide enrichment
Authors: Zhang B. , Yu R. Z. , Yu Y. H. , Peng C. , Xie R. , Zhang Y. , Chen J. Y.
Published: October 2018

Lectin inspired polymers polySD-SiO2were prepared and applied to the high-efficiency enrichment of glycopeptides.
A novel and accurate microfluidic assay of CD62L in bladder cancer serum samples
Authors: Phadke Gayatri S. , Satterwhite-Warden Jennifer E. , Choudhary Dharamainder , Taylor John A. , Rusling James F.
Published: October 2018

A magnetic bead-based, microfluidic immunoarray of CD62L can distinguish between low- and high-grade bladder cancer tumors.
Correction: The mechanism and regularity of quenching the effect of bases on fluorophores: the base-quenched probe method
Authors: Mao Huihui , Luo Guanghua , Zhan Yuxia , Zhang Jun , Yao Shuang , Yu Yang
Published: October 2018

Correction for ‘The mechanism and regularity of quenching the effect of bases on fluorophores: the base-quenched probe method’ by Huihui Mao et al., Analyst, 2018, 143, 3292–3301.
High-tap density LiFePO4 microsphere developed by combined computational and experimental approaches
Authors: Jin Yuan , Tang Xincun , Wang Yang , Dang Wei , Huang Jie , Fang Xiong
Published: October 2018

The lithiation/delithiation in LiFePO4 is mainly anisotropic with lithium-ion diffusion being mainly limited to channels along the b-axis.
Interpenetrated nano-MOFs for ultrahigh-performance supercapacitors and excellent dye adsorption performance
Authors: Wang Kuaibing , Wang Xin , Zhang Dan , Wang Huijian , Wang Zikai , Zhao Minyan , Xi Rui , Wu Hua , Zheng Mingbo
Published: October 2018

Designing and preparing kinetically stable metal–organic frameworks through ligand functionalization can effectively improve their supercapacitive performances.
Guest-induced reversible crystal-to-amorphous-to-crystal transformation in a Co(ii)-based metal–organic framework
Authors: Tan Huiling , Chen Qibin , Sheng Yujie , Li Xiaoxiao , Liu Honglai
Published: October 2018

A crystal-to-amorphous-to-crystal (CAC) transformation was obtained during the dehydration/rehydration process. Moreover, an amorphous sample DPPB-2 could separate methanol and ethanol from other VOCs.
Synthesis and phase transformation of NaGdF4:Yb–Er thin films using electro-deposition method at moderate temperatures
Authors: Jia Hong , Zhou Yiping , Li Xue , Li Yan , Zhang Weiying , Fu Hongzhi , Zhao Jianguo , Pan Liuzhan , Liu Xiaofeng , Qiu Jianrong
Published: October 2018

Herein, a thin film of hexagonal-phase NaGdF4:Yb–Er is fabricated by electro-deposition at moderate temperatures. The phase of NaGdF4:Yb–Er thin film can be controlled by adding PVP in the electrolyte.
Charge separation at an organic/inorganic nano-hybrid interface: atomistic simulations of a para-sexiphenyl ZnO system
Authors: Plehn Thomas , Ziemann Dirk , May Volkhard
Published: October 2018

A prototypical organic/inorganic interface is considered which is formed by vertical stacking of 20 para-sexiphenyl molecules physisorbed on a ZnO nano-cluster of 3903 atoms.
Chemically driven surface effects in polar intermetallic topological insulators A3Bi
Authors: Rusinov I. P. , Golub P. , Sklyadneva I. Yu. , Isaeva A. , Menshchikova T. V. , Echenique P. M. , Chulkov E. V.
Published: October 2018

Surface electronic spectra, surface and bulk properties as well as the underlying chemical bonding characteristics in topological insulators with complex bonding patterns are considered for the example of cubic, polar intermetallics KNa2Bi, K3Bi and Rb3Bi (with the general formula A3Bi, A – alkali metal).
Analysis of charge transfer transitions in stacked π-electron donor–acceptor complexes
Authors: Cui Zhong-hua , Aquino Adélia J. A. , Sue Andrew C.-H. , Lischka Hans
Published: October 2018

Molecular orbitals involved in the charge-transfer transition from 1,5-diaminonaphthalene to pyromellitic diimide.
Fine tuning of electron transfer and spin chemistry parameters in triarylamine–bridge–naphthalene diimide dyads by bridge substituents
Authors: Schäfer Julian , Holzapfel Marco , Schmiedel Alexander , Steiner Ulrich E. , Lambert Christoph
Published: October 2018

A series of donor–acceptor dyads with diverse meta-conjugated benzene bridges show a pronounced magnetic field dependent charge recombination.