bluuebunny/crossref_metadata_2025 huggingface dataset:
A de novo mutation in the EXT2 gene associated with osteochondromatosis in a litter of American Staffordshire Terriers
Authors: Friedenberg Steven G. , Vansteenkiste Daniella , Yost Oriana , Treeful Amy E. , Meurs Kathryn M. , Tokarz Debra A. , Olby Natasha J.
Published: February 2018

Background

We aimed to identify mutations associated with osteochondromatosis in a litter of American Staffordshire Terrier puppies.

Hypothesis

We hypothesized that the associated mutation would be located in a gene that causes osteochondromatosis in humans.

Animals

A litter of 9 American Staffordshire puppies, their sire and dam, 3 of 4 grandparents, 26 healthy unrelated American Staffordshire Terriers, and 154 dogs of 27 different breeds.

Methods

Whole genome sequencing was performed on the proband, and variants were compared against polymorphisms derived from 154 additional dogs across 27 breeds, as well as single nucleotide polymorphism database 146. One variant was selected for follow‐up sequencing. Parentage and genetic mosaicism were evaluated across the litter.

Results

We found 56,301 genetic variants unique to the proband. Eleven variants were located in or near the gene exostosin 2 (EXT2), which is strongly associated with osteochondromatosis in humans. One heterozygous variant (c.969C > A) is predicted to result in a stop codon in exon 5 of the gene. Sanger sequencing identified the identical mutation in all affected offspring. The mutation was absent in the unaffected offspring, both parents, all available grandparents, and 26 healthy unrelated American Staffordshire Terriers.

Conclusions and Clinical Importance

These findings represent the first reported mutation associated with osteochondromatosis in dogs. Because this mutation arose de novo, the identical mutation is unlikely to be the cause of osteochondromatosis in other dogs. However, de novo mutations in EXT2 are common in humans with osteochondromatosis, and by extension, it is possible that dogs with osteochondromatosis could be identified by sequencing the entire EXT2 gene.
Hyphal induction under the condition without inoculation in Candida albicans is triggered by Brg1‐mediated removal of NRG1 inhibition
Authors: Su Chang , Yu Jing , Sun Qiangqiang , Liu Qian , Lu Yang
Published: February 2018

Candida albicans can switch between yeast and hyphae growth forms, which is critical for its pathogenesis. Diluting from saturated cells into fresh medium at 37°C is routinely used to induce hyphae, which depends on the cAMP‐PKA pathway‐activated transcriptional down‐regulation of NRG1 and degradation of Nrg1 protein triggered by inoculation. It is reported that N‐acetylglucosamine (GlcNAc), serum or neutral pH could stimulate filamentation in log phase cells, whereas how C. albicans develops hyphae without inoculation remains unknown. Here, we show that NRG1 down‐regulation is necessary for hyphal growth under this condition. Instead of cAMP‐PKA pathway, GlcNAc sensor Ngs1 is responsible for the down‐regulation of NRG1 upon GlcNAc induction in log phase cells through its N‐acetyltransferase activity. From a genetic screen, Brg1 is found to be essential for hyphal development without inoculation. Ngs1 binds to BRG1 promoter to induce its expression in GlcNAc. Importantly, constitutively expressed BRG1 induces NRG1 down‐regulation even in the absence of GlcNAc or Ngs1. Serum or neutral pH‐induced filamentation in log phase cells is also through Brg1‐mediated NRG1 down‐regulation. Our study provides a molecular mechanism for how C. albicans forms hyphae in different cell states. This flexibility may facilitate C. albicans to adapt varied host environment during infection.
Intentional tracheoesophageal fistula cannulation for gastric decompression in type C esophageal atresia
Authors: Papoff Paola , Cicchetti Roberto , Montecchia Francesco , Midulla Fabio , Ceccanti Silvia , Cozzi Denis
Published: February 2018

We describe a nonsurgical technique for managing gastric distention in infants with type C esophageal atresia, involving intubating the trachea with an umbilical catheter and entering the stomach through the fistula as soon as a flexible bronchoscope found its wide‐open orifice. This technique might have a special role when gastric distention precedes other commonly used preventive measures.
Distances from vocal cords to mid‐trachea for optimizing endotracheal tubes depth markers according to gestational age
Authors: Rigo Vincent , Fayoux Pierre
Published: February 2018

Background

Adequate endotracheal tube positioning in preterm infants is complicated by the short length of the airway. Distal markers were designed to help with the insertion of endotracheal tubes at an appropriate depth below the vocal cords. However, those markers are not standardized between manufacturers, each tube size displays only one (sometimes 2) markers to provide information for infants of various gestational ages, and indicated distances are often too long for extremely preterm infants.

Aims

The study aims to describe vocal cords to mid‐tracheal distance for different gestational ages and determine if depth markers should be adjusted accordingly.

Methods

Half the tracheal length added to the height of the posterior lamina of the cricoids approximates the distance between vocal cords and mid‐trachea. Those dimensions were retrospectively retrieved from a database of laryngo‐tracheal measurements obtained during autopsies of fetuses and newborn infants free of upper airway malformations. The equation of correlation between gestational age and distance from vocal cords to mid‐trachea was used to calculate those distances for different gestational ages.

Results

Data were derived from 114 patients. Vocal cords to mid‐trachea distance is linearly correlated with gestational age (r = .90; distance = 2.831 + 0.6208 × gestational age). We suggest depth markers at 17.7, 19.0, 20.8, 22.7, 24.6, and 26.4 mm for gestational ages of 24, 26, 29, 32, 35, and 38 weeks, respectively, indicated by contrasting colors.

Conclusion

The linear relationship between laryngo‐tracheal size and gestational age offers the opportunity to revise endotracheal tube depth markers for the smallest patients. Trials comparing those suggested markers with those currently in use are needed before implementation.
Sensitivity of chickpea and faba bean to root‐zone hypoxia, elevated ethylene, and carbon dioxide
Authors: Munir Rushna , Konnerup Dennis , Khan Hammad A. , Siddique Kadambot H.M. , Colmer Timothy D.
Published: February 2018

During soil waterlogging, plants experience O2 deficits, elevated ethylene, and high CO2 in the root‐zone. The effects on chickpea (Cicer arietinum L.) and faba bean (Vicia faba L.) of ethylene (2 μL L−1), CO2 (2–20% v/v) or deoxygenated stagnant solution were evaluated. Ethylene and high CO2 reduced root growth of both species, but O2 deficiency had the most damaging effect and especially so for chickpea. Chickpea suffered root tip death when in deoxygenated stagnant solution. High CO2 inhibited root respiration and reduced growth, whereas sugars accumulated in root tips, of both species. Gas‐filled porosity of the basal portion of the primary root of faba bean (23%, v/v) was greater than for chickpea (10%), and internal O2 movement was more prominent in faba bean when in an O2‐free medium. Ethylene treatment increased the porosity of roots. The damaging effects of low O2, such as death of root tips, resulted in poor recovery of root growth upon reaeration. In conclusion, ethylene and high CO2 partially inhibited root extension in both species, but low O2 in deoxygenated stagnant solution had the most damaging effect, even causing death of root tips in chickpea, which was more sensitive to the low O2 condition than faba bean.
Modified triangular hepatic vein reconstruction for preventing hepatic venous outflow obstruction in pediatric living donor liver transplantation using left lateral segment grafts
Authors: Fukuda Akinari , Sakamoto Seisuke , Sasaki Kengo , Narumoto Soichi , Kitajima Toshihiro , Hirata Yoshihiro , Hishiki Tomoro , Kasahara Mureo
Published: February 2018

HVOO can be a critical complication in pediatric LDLT. The aim of this study was to evaluate a modified triangular technique of hepatic vein reconstruction for preventing HVOO in pediatric LDLT. A total of 298 pediatric LDLTs were performed using a left lateral segment graft by 2 methods for reconstruction of the hepatic vein. In 177 recipients, slit‐shaped anastomosis was indicated with partial clamp of the IVC. A total of 121 recipients subjected to the modified triangular anastomosis with total clamp of the IVC. We compared the incidence of hepatic vein anastomotic complications between these 2 methods. Nine of the 177 cases (5.3%) treated with the conventional technique were diagnosed with outflow obstruction. All 9 cases underwent hepatic vein reconstruction with the slit‐shaped hepatic vein anastomosis. In contrast, there were no cases of outflow obstruction in the 121 cases treated with the modified triangular anastomosis. The modified triangular technique of hepatic vein reconstruction with total clamping of the IVC was useful for preventing HVOO in pediatric LDLT.
Nonlinear Optical Microscopy for Melanoma: Challenges, Tools and Opportunities
Authors: Evans Conor L.
Published: February 2018

The natural pigments known as melanins are thought to play a role in the etiology and progression of melanoma, but many of their roles are currently not well understood. While quantification of melanins have, up until now, have been performed in bulk tissue ex vivo, new imaging technologies have unlocked the means to visualize and quantify melanins at the sub‐cellular scale. The nonlinear imaging methods known as pump‐probe, coherent Raman, and sum‐frequency absorption microscopies provide subcellular resolution imaging of melanins, enabling label‐free, longitudinal quantification of both eumelanin and pheomelanin in situ and in vivo. These nonlinear imaging toolkits have been well proven in both animal models and human samples, moving them tantalizingly close to clinical application. Future efforts integrating these tools into practical, mobile imaging systems will provide immense benefit both to clinical research and practice.
Survey of viruses infecting open‐field pepper crops in Côte d'Ivoire and diversity of Pepper veinal mottle virus and Cucumber mosaic virus
Authors: Bolou Bi B. A. , Moury B. , Abo K. , Sorho F. , Cherif M. , Girardot G. , Kouassi N. P. , Kone D.
Published: February 2018

The prevalence of viruses in pepper crops grown in open fields in the different agro‐ecological zones (AEZs) of Côte d'Ivoire was surveyed. Pepper veinal mottle virus (PVMV; genus Potyvirus) and Cucumber mosaic virus (CMV; genus Cucumovirus) were the most frequent viruses among those surveyed, while tobamoviruses (genus Tobamovirus) were detected at low frequency. PVMV showed a high heterogeneity across AEZs, which may be related to climatic, ecological or agronomical conditions, whereas CMV was more homogeneously distributed. The molecular diversity of CMV and PVMV were analysed from partial genome sequences. Despite the low number of CMV isolates characterized, two molecular groups were revealed, one corresponding to subgroup IA and the other to reassortants between subgroups IA and IB. RNAs 1 and 3 of the reassortants clustered with the IB subgroup of CMV isolates, whereas their RNA 2 clustered with the IA subgroup. Importantly, RNA 1 of CMV isolates of the IB subgroup has been shown to be responsible for adaptation to pepper resistance. The diversity of PVMV in the VPg‐ and coat protein‐coding regions revealed multiple clades. The central part of the VPg showed a high level of amino acid diversity and evidence of positive selection, which may be a signature of adaptation to plant recessive resistance. As a consequence, for efficient deployment of resistant pepper cultivars, it would be desirable to examine the occurrence of virulent isolates in the CMV or PVMV populations in Côte d'Ivoire and to follow their evolution as the resistance becomes more widely deployed.
Alveolar ridge preservation in the esthetic zone
Authors: Jung Ronald E. , Ioannidis Alexis , Hämmerle Christoph H. F. , Thoma Daniel S.
Published: February 2018

In the esthetic zone, in the case of tooth extraction, the clinician is often confronted with a challenge regarding the optimal decision‐making process for providing a solution using dental implants. This is because, after tooth extraction, alveolar bone loss and structural and compositional changes of the covering soft tissues, as well as morphological alterations, can be expected. Ideally, the therapeutic plan starts before tooth extraction and it offers three options: spontaneous healing of the extraction socket; immediate implant placement; and techniques for preserving the alveolar ridge at the site of tooth removal. The decision‐making process mainly depends on: (i) the chosen time‐point for implant placement and the ability to place a dental implant; (ii) the quality and quantity of soft tissue in the region of the extraction socket; (iii) the remaining height of the buccal bone plate; and (iv) the expected rates of implant survival and success. Based on scientific evidence, three time‐periods for alveolar ridge preservation are described in the literature: (i) soft‐tissue preservation with 6–8 weeks of healing after tooth extraction (for optimization of the soft tissues); (ii) hard‐ and soft‐tissue preservation with 4–6 months of healing after tooth extraction (for optimization of the hard and soft tissues); and (iii) hard‐tissue preservation with > 6 months of healing after tooth extraction (for optimization of the hard tissues).
No Right to Classified Public Whistleblowing
Authors: Boot Eric R.
Published: February 2018

Given the crucial role unauthorized disclosures can play in uncovering grave government wrongdoing, it makes sense to search for a defense of justified cases of what I call “classified public whistleblowing.” The question that concerns me is what form such a defense should take. The main claim will be a negative one, namely, that a defense of whistleblowing cannot be based on individualrights, be they legal or moral, though this is indeed the most commonly proposed defense. In closing, I will outline a more appealing alternative, namely, a justification defense.
Coordination Cannot Establish Political Authority
Authors: Brinkmann Matthias
Published: February 2018

One of the most common arguments in favour of the state's authority is that without the coordinating hand of political institutions, we could not achieve important moral benefits. I argue that if we understand authority correctly, then coordination cannot evenin principleestablish that coordinators have political authority.
The People and Populism
Authors: Zaccaria Giuseppe
Published: February 2018

“What is and what is defined as populism?” In response to this question the best political theories and philosophies have put forward many different answers, that are taken into account in this article. The article affirms the constitutive ambiguity of the concept of “populism” and its ability to unify very different issues. After analyzing some of the implications that populism entails in practice (in particular the political use of fear and the emphasis on the role of the citizens' anxieties because of migratory flows, the spiral of fear and insecurity triggered by terrorism, the role of religions as symbolic repertoires), the article stresses the link between populism and the end of the logic of the principle of representation, specific of the liberal and democratic theories. The emphasis on the role of the “people” in opposition to the political elites is also a feature of populism, analyzed by the author in this article. In conclusion, the author focuses on the legal field: some of the contemporary constitutional theories, in particular the so‐called “popular constitutionalism”, are discussed. These theories, while polemicizing with those authors who overestimate the role of the Supreme Court, reassess the function of the average citizen in the life of constitutional culture, with the intent of favouring greater political participation and strengthening democratic life.
A potential method for improving coral self‐attachment
Authors: Tagliafico Alejandro , Rangel Salomé , Christidis Leslie , Kelaher Brendan P.
Published: February 2018

Coral restoration is becoming increasingly important to sustain declining reefs. The survival rate of translocated corals in restoration projects is around 65%. This rate is, however, highly variable among projects, with success ranging from 0 to 90% and with detachment being a significant cause of mortality. Improving the speed and strength of coral self‐attachment would increase survivorship in translocated corals. To address this need, we tested whether fragments of the scleractinian coral Hydnophora rigida, artificially attached upside‐down, would self‐attach more rapidly to the substratum than those artificially attached the right way up, which is the normal practice. We also tested the effect of three different diets (unfed, normal Artemia, and lipid‐enriched Artemia) on coral growth and other biological responses. After 100 days, our results demonstrated that corals fixed upside‐down grew significantly wider and faster over the substratum than corals fixed the right way up. A significantly higher number of fragments fixed upside‐down were also able to self‐attach and grow over the substratum (87%) compared with fragments fixed the right way up (58%). Neither the buoyant weight, height increment, symbiont density, chlorophyll, maximum quantum yield nor color of corals fixed upside‐down differed significantly from corals fixed the right way up. Our data show that simply inverting the orientation of coral fragments may substantially accelerate the time for self‐attachment and increase the survival rate of translocated corals in restoration projects.
The DHS Program's Modeled Surfaces Spatial Datasets
Authors: Burgert‐Brucker Clara R. , Dontamsetti Trinadh , Gething Peter W.
Published: February 2018

Spatially interpolated map surface datasets for key development indicators are being produced and publicly shared using population‐based surveys from the USAID‐funded Demographic and Health Survey (DHS) Program. Each modeled surface is produced with standardized geostatistical modeling methods. For each indicator, a package is available that includes spatial raster grids of 5 × 5 km pixels for the point estimate surface and an uncertainty surface, along with validation statistics and other model diagnostic data. The maps are publicly available for download on the DHS Program Spatial Data Repository at http://spatialdata.dhsprogram.com/. The modeled surfaces are produced with publicly available geo‐referenced data on each indicator as collected by the DHS Program, augmented with other relevant spatial data sources that act as covariates. A Bayesian model−based geostatistical (MBG) approach is used to generate the modeled surfaces. Spatially modeled surfaces can be used to support and improve decision‐making at multiple levels within many development programs including health, population, family planning, nutrition, and water and sanitation. The modeled surfaces can be used in their original 5 × 5 km pixel format, operationalized to other geographic areas as relevant for the program, or linked to DHS or other survey data for additional analysis.
Hypoxia induces production of citrullinated proteins in human fibroblast‐like synoviocytes through regulating HIF1α
Authors: Yu R. , Li C. , Sun L. , Jian L. , Ma Z. , Zhao J. , Liu X.
Published: February 2018

Hypoxia is a prominent microenvironment feature in a range of disorders including cancer, rheumatoid arthritis (RA), atherosclerosis, inflammatory bowel disease (IBD), infection and obesity. Hypoxia promotes biological functions of fibroblast‐like synoviocytes via regulating hypoxia‐inducible factor 1α (HIF1α). Dysregulated protein citrullination in RA drives the production of antibodies to citrullinated proteins, a highly specific biomarker of RA. However, the mechanisms promoting citrullination in RA are not yet fully elucidated. In this study, we investigated whether pathophysiological hypoxia as found in the rheumatoid synovium modulates the citrullination in human fibroblast‐like synoviocytes (HFLS). Here, we found that peptidylarginine deiminase 2 (PAD2) and citrullinated proteins were increased in HFLS after exposure to hypoxia. Moreover, knocking down HIF1α by HIF1α siRNA ameliorated the expression of PAD2 and citrullinated proteins. Collectively, this study provides a new mechanism involved in generating citrullinated proteins: hypoxia promotes citrullination and PAD production in HFLS. Concurrently, we also proposed a novel hypoxia involved mechanism in RA pathogenesis. This study deepens our understanding of the role of hypoxia in the pathogenesis of RA and provides a potential therapeutic strategy for RA.
Endogenous protein and enzyme fragments induce immunoglobulin E‐independent activation of mast cells via a G protein‐coupled receptor,MRGPRX2
Authors: Tatemoto K. , Nozaki Y. , Tsuda R. , Kaneko S. , Tomura K. , Furuno M. , Ogasawara H. , Edamura K. , Takagi H. , Iwamura H. , Noguchi M. , Naito T.
Published: February 2018

Mast cells play a central role in inflammatory and allergic reactions by releasing inflammatory mediators through 2 main pathways, immunoglobulin E‐dependent and E‐independent activation. In the latter pathway, mast cells are activated by a diverse range of basic molecules (collectively known as basic secretagogues) through Mas‐related G protein‐coupled receptors (MRGPRs). In addition to the known basic secretagogues, here, we discovered several endogenous protein and enzyme fragments (such as chaperonin‐10 fragment) that act as bioactive peptides and induce immunoglobulin E‐independent mast cell activation viaMRGPRX2 (previously known as MrgX2), leading to the degranulation of mast cells. We discuss the possibility thatMRGPRX2 responds various as‐yet‐unidentified endogenous ligands that have specific characteristics, and propose thatMRGPRX2 plays an important role in regulating inflammatory responses to endogenous harmful stimuli, such as protein breakdown products released from damaged or dying cells.
The Emergence, Articulation and Negotiation of a New Food Industry Initiative in Rural Australia: Boundary Object, Organisation or Triple Helix Model?
Authors: Betzold Alana , Carew Anna L. , Lewis Gemma K. , Lovell Heather
Published: February 2018

This article reports on research to track and trace the development and diffusion of a new initiative for clustering a diverse range of agro‐food businesses located in the rural state of Tasmania, Australia. The initiative is termed ‘FermenTasmania’. To structure our analysis, our research team leveraged the concepts of boundary objects and organisations, and the Triple Helix model of innovation; testing these sociological concepts and model as a means to explain the nature, structure and emerging trajectory of FermenTasmania. This paper aims to contribute two distinct, but related findings: first, analysis of the fit and utility of the aforementioned concepts and model to track the emergence of FermenTasmania; and, second, assessment of the dynamics of innovation regarding the formation of this new social entity bridging agriculture and tourism in a rural area, with particular attention to the role of place.
Concentration behavior of the penalized least squares estimator
Authors: Muro Alan , van de Geer Sara
Published: February 2018

Consider the standard nonparametric regression model and take as estimator the penalized least squares function. In this article, we study the trade‐off between closeness to the true function and complexity penalization of the estimator, where complexity is described by a seminorm on a class of functions. First, we present an exponential concentration inequality revealing the concentration behavior of the trade‐off of the penalized least squares estimator around a nonrandom quantity, where such quantity depends on the problem under consideration. Then, under some conditions and for the proper choice of the tuning parameter, we obtain bounds for this nonrandom quantity. We illustrate our results with some examples that include the smoothing splines estimator.
A spatial‐knowledge‐enhanced heuristic for solving the p‐median problem
Authors: Mu Wangshu , Tong Daoqin
Published: February 2018

The p‐median problem (PMP) is one of the most applied location problems in urban and regional planning. As an NP‐hard problem, the PMP remains challenging to solve optimally, especially for large‐sized problems. A number of heuristics have been developed to obtain PMP solutions in a fast manner. Among the heuristics, the Teitz and Bart (TB) algorithm has been found effective for finding high‐quality solutions. In this article, we present a spatial‐knowledge‐enhanced Teitz and Bart (STB) heuristic method for solving PMPs. The STB heuristic prioritizes candidate facility sites to be examined in the solution set based on the spatial distribution of demand and service provision. Tests based on a range of PMPs demonstrate the effectiveness of the STB heuristic. This new algorithm can be incorporated into current commercial GIS packages to solve a wide range of location‐allocation problems.
Mapping hourly dynamics of urban population using trajectories reconstructed from mobile phone records
Authors: Liu Zhang , Ma Ting , Du Yunyan , Pei Tao , Yi Jiawei , Peng Hui
Published: February 2018

Understanding the spatiotemporal dynamics of urban population is crucial for addressing a wide range of urban planning and management issues. Aggregated geospatial big data have been widely used to quantitatively estimate population distribution at fine spatial scales over a given time period. However, it is still a challenge to estimate population density at a fine temporal resolution over a large geographical space, mainly due to the temporal asynchrony of population movement and the challenges to acquiring a complete individual movement record. In this article, we propose a method to estimate hourly population density by examining the time‐series individual trajectories, which were reconstructed from call detail records using BP neural networks. We first used BP neural networks to predict the positions of mobile phone users at an hourly interval and then estimated the hourly population density using log‐linear regression at the cell tower level. The estimated population density is linearly correlated with population census data at the sub‐district level. Trajectory clustering results show five distinct diurnal dynamic patterns of population movement in the study area, revealing spatially explicit characteristics of the diurnal commuting flows, though the driving forces of the flows need further investigation.
In vitro evaluation of a simulated pneumoperitoneum environment using carbon dioxide on canine transitional cell carcinoma
Authors: Asthana Rashi , Oblak Michelle L. , Singh Ameet , Mutsaers Anthony J.
Published: February 2018

Objective

To assess the impact of a simulated CO2 pneumoperitoneum environment on the viability and proliferation of canine transitional cell carcinoma (TCC) cells in vitro.

Study design

In vitro study.

Methods

A control Madin‐Darby canine kidney (MDCK) cell line and 3 canine TCC cell lines were exposed to 100% CO2 at pressure of 0, 5, 10, or 15 mmHg for 2 hours by using an airtight chamber and a mechanical insufflator at 37°C. Culture media pH was measured. Viability and proliferation were assessed by using a resazurin assay and trypan blue dye, respectively.

Results

The pH in the media significantly decreased immediately after CO2 exposure but returned to normal within 1 hour. The viability of the cell lines was variably affected at the evaluated pressures. Insufflation pressure of 10 mmHg resulted in significantly decreased cell viability compared with control. The impact of 15 mmHg CO2 was comparable to 0 mmHg and control. CO2 insufflation pressure had no significant effects on proliferation up to 7 days postexposure.

Conclusion/Clinical significance: A positive pressure CO2 environment significantly decreased the viability of TCC and MDCK cells under specific conditions without influencing their proliferation up to 7 days postexposure. Investigating these effects in clinical patients undergoing CO2 laparoscopy is essential to assess for port site metastasis or peritoneal carcinomatosis in order to translate these in vitro results to clinical recommendations.
Effect Analysis of Real Estate Price and Monetary Policy: An Empirical Study Based on China Macroeconomic Data
Authors: Su Liang , Lin Li , Chen Shaozhen , Li Lin
Published: February 2018

Since the reform of the housing system in 1998, China's real estate market has been gradually marketized. A large number of demand-side purchases that were suppressed by the planned economy were released. The rapidly rising real estate prices affected the People's Bank of China's monetary policy through Tobin's Q and the financial accelerator. This paper establishes a VAR model to analyze the policy factors and find out “land finance” has promoted the rise of real estate prices to a certain extent and the regulation of the real estate market lags behind; real estate prices can interfere with the effect of monetary policy which rising real estate prices increase the uncertainty of monetary policy. Finally, this paper puts forward policy suggestions of the monetary policy and local fiscal revenue.
The dual‐gate model for pentameric ligand‐gated ion channels activation and desensitization
Authors: Gielen Marc , Corringer Pierre‐Jean
Published: February 2018

Pentameric ligand‐gated ion channels (pLGICs) mediate fast neurotransmission in the nervous system. Their dysfunction is associated with psychiatric, neurological and neurodegenerative disorders such as schizophrenia, epilepsy and Alzheimer's disease. Understanding their biophysical and pharmacological properties, at both the functional and the structural level, thus holds many therapeutic promises. In addition to their agonist‐elicited activation, most pLGICs display another key allosteric property, namely desensitization, in which they enter a shut state refractory to activation upon sustained agonist binding. While the activation mechanisms of several pLGICs have been revealed at near‐atomic resolution, the structural foundation of desensitization has long remained elusive. Recent structural and functional data now suggest that the activation and desensitization gates are distinct, and are located at both sides of the ion channel. Such a ‘dual gate mechanism’ accounts for the marked allosteric effects of channel blockers, a feature illustrated herein by theoretical kinetics simulations. Comparison with other classes of ligand‐ and voltage‐gated ion channels shows that this dual gate mechanism emerges as a common theme for the desensitization and inactivation properties of structurally unrelated ion channels.

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In situ characterization of the deposition of anatase TiO2 on rutile TiO2(110)
Authors: Head Ashley R. , Johansson Niclas , Niu Yuran , Snezhkova Olesia , Chaudhary Shilpi , Schnadt Joachim , Bluhm Hendrik , Chen Chaoyu , Avila José , Asensio Maria-Carmen
Published: February 2018

Growing additional TiO2 thin films on TiO2 substrates in ultrahigh vacuum (UHV)-compatible chambers have many applications for sample preparation, such as smoothing surface morphologies, templating, and covering impurities. However, there has been little study into how to control the morphology of TiO2 films deposited onto TiO2 substrates, especially using atomic layer deposition (ALD) precursors. Here, the authors show the growth of a TiO2 film on a rutile TiO2(110) surface using titanium tetraisopropoxide (TTIP) and water as the precursors at pressures well below those used in common ALD reactors. X-ray absorption spectroscopy suggests that the relatively low sample temperature (175 °C) results in an anatase film despite the rutile template of the substrate. Using ambient pressure x-ray photoelectron spectroscopy, the adsorption of TTIP was found to be self-limiting, even at room temperature. No molecular water was found to adsorb on the surface. The deposited thickness suggests that an alternate chemical vapor deposition growth mechanism may be dominating the growth process. This study highlights the possibility that metal oxide film deposition from molecular precursors is an option for sample preparations in common UHV-compatible chambers.
Elucidation of ALD MgZnO deposition processes using low energy ion scattering
Authors: Werner Matthew , Roberts Joseph W. , Potter Richard J. , Dawson Karl , Chalker Paul R.
Published: February 2018

Low energy ion scattering (LEIS) provides an analytical tool for probing the surface composition and structure on the angstrom to nanometer scale. These length scales are central to the growth and processing of ultrathin films produced by atomic layer deposition (ALD). Here, the authors present the application of LEIS to the elucidation of ALD deposition processes and in particular how it provides information about growth parameters including the growth per cycle (GPC), the nature of the film–substrate interfaces, and adatom incorporation into the growing film. The deposition of varying thickness zinc oxide films and the composition of magnesium-doped zinc oxide films are used as model systems. LEIS has been used to investigate the GPC of ZnO using two approaches, namely, static and dynamic measurements. The static approach exploits inelastic energy loss processes to estimate the GPC of different thicknesses of ZnO films. The dynamic approach measures the GPC via a combination of LEIS surface analysis and sputter depth profiling. The measurement of GPC using these two methods is compared with spectroscopic ellipsometry. The adatom incorporation of Mg into the ZnO matrix is measured using a dynamic LEIS process, and the variation of Mg incorporation is discussed as a function of the varying ALD cycle fractions of Mg and ZnO used to deposit MgxZn1-xO films in the range of 0 < x < 1.
Macronutrient Intakes of Male Rugby Union Players: A Review
Authors: Black Katherine Elizabeth , Black Alistair David , Baker Dane Frances
Published: February 2018

Rugby is a worldwide intermittent team sport. Players tend to be heavier than the majority of similar team sport athletes on whom the dietary guidelines have been developed. Therefore, the aim of the current review was to describe the intakes of rugby union players. Article databases were searched up to February 2017 and were included if they were published in English and reported dietary intakes of male rugby union players. Of the research articles identified, energy intakes were lower than two of three studies that reported intakes and expenditure, which would suggest the players were losing weight that is somewhat supported by the decreases in skinfolds seen during preseason. However, it should also be noted that there are errors in both the measurement of energy intakes and expenditure. Carbohydrate intakes ranged from 2.6 to 6.5 g·kg−1·day−1, which is lower than the current relative to body mass recommendations; however, this would not be classed as a low-carbohydrate diet. The consistently low intakes of carbohydrate suggest that these intake levels maybe sufficient for performance, given the players greater body mass or there are errors in the measurements. However, there is currently no evidence for the carbohydrate needs of rugby union players in terms of performance. The lower intakes than expenditure would suggest the players were losing weight. Previous research shows that rugby union players lose body fat during preseason training.
Convergence of Wnt, growth factor, and heterotrimeric G protein signals on the guanine nucleotide exchange factor Daple
Authors: Aznar Nicolas , Ear Jason , Dunkel Ying , Sun Nina , Satterfield Kendall , He Fang , Kalogriopoulos Nicholas A. , Lopez-Sanchez Inmaculada , Ghassemian Majid , Sahoo Debashis , Kufareva Irina , Ghosh Pradipta
Published: February 2018

The protein Daple coordinates cross-talk among growth factor receptors, Wnt, and G protein–coupled signaling pathways to facilitate tumor progression.
Long-Term Exposure of Agricultural Soil to Veterinary Antibiotics Changes the Population Structure of Symbiotic Nitrogen-Fixing Rhizobacteria Occupying Nodules of Soybeans (Glycine max)
Authors: Revellin Cécile , Hartmann Alain , Solanas Sébastien , Topp Edward
Published: February 2018

Antibiotics are entrained in agricultural soil through the application of manures from medicated animals. In the present study, a series of small field plots was established in 1999 that receive annual spring applications of a mixture of tylosin, sulfamethazine, and chlortetracycline at concentrations ranging from 0.1 to 10 mg · kg
−1
soil. These antibiotics are commonly used in commercial swine production. The field plots were cropped continuously for soybeans, and in 2012, after 14 annual antibiotic applications, the nodules from soybean roots were sampled and the occupying bradyrhizobia were characterized. Nodules and isolates were serotyped, and isolates were distinguished using 16S rRNA gene and 16S to 23S rRNA gene intergenic spacer region sequencing, multilocus sequence typing, and RSα fingerprinting. Treatment with the antibiotic mixture skewed the population of bradyrhizobia dominating the nodule occupancy, with a significantly larger proportion of
Bradyrhizobium liaoningense
organisms even at the lowest dose of 0.1 mg · kg
−1
soil. Likewise, all doses of antibiotics altered the distribution of RSα fingerprint types. Bradyrhizobia were phenotypically evaluated for their sensitivity to the antibiotics, and there was no association between
in situ
treatment and a decreased sensitivity to the drugs. Overall, long-term exposure to the antibiotic mixture altered the composition of bradyrhizobial populations occupying nitrogen-fixing nodules, apparently through an indirect effect not associated with the sensitivity to the drugs. Further work evaluating agronomic impacts is warranted.

IMPORTANCE
Antibiotics are entrained in agricultural soil through the application of animal or human waste or by irrigation with reused wastewater. Soybeans obtain nitrogen through symbiotic nitrogen fixation. Here, we evaluated the impact of 14 annual exposures to antibiotics commonly used in swine production on the distribution of bradyrhizobia occupying nitrogen-fixing nodules on soybean roots in a long-term field experiment. By means of various sequencing and genomic fingerprinting techniques, the repeated exposure to a mixture of tylosin, sulfamethazine, and chlortetracycline each at a nominal soil concentration of 0.1 mg · kg
−1
soil was found to modify the diversity and identity of bradyrhizobia occupying the nodules. Nodule occupancy was not associated with the level of sensitivity to the antibiotics, indicating that the observed effects were not due to the direct toxicity of the antibiotics on bradyrhizobia. Altogether, these results indicate the potential for long-term impacts of antibiotics on this agronomically important symbiosis.
Butenolides from Streptomyces albus J1074 Act as External Signals To Stimulate Avermectin Production in Streptomyces avermitilis
Authors: Nguyen Thao Bich , Kitani Shigeru , Shimma Shuichi , Nihira Takuya
Published: February 2018

In streptomycetes, autoregulators are important signaling compounds that trigger secondary metabolism, and they are regarded as
Streptomyces
hormones based on their extremely low effective concentrations (nM) and the involvement of specific receptor proteins. Our previous distribution study revealed that butenolide-type
Streptomyces
hormones, including avenolide, are a general class of signaling molecules in streptomycetes and that
Streptomyces albus
strain J1074 may produce butenolide-type
Streptomyces
hormones. Here, we describe metabolite profiling of a disruptant of the
S. albus
aco
gene, which encodes a key biosynthetic enzyme for butenolide-type
Streptomyces
hormones, and identify four butenolide compounds from
S. albus
J1074 that show avenolide activity. The compounds structurally resemble avenolide and show different levels of avenolide activity. A dual-culture assay with imaging mass spectrometry (IMS) analysis for
in vivo
metabolic profiling demonstrated that the butenolide compounds of
S. albus
J1074 stimulate avermectin production in another
Streptomyces
species,
Streptomyces avermitilis
, illustrating the complex chemical interactions through interspecies signals in streptomycetes.

IMPORTANCE
Microorganisms produce external and internal signaling molecules to control their complex physiological traits. In actinomycetes,
Streptomyces
hormones are low-molecular-weight signals that are key to our understanding of the regulatory mechanisms of
Streptomyces
secondary metabolism. This study reveals that acyl coenzyme A (acyl-CoA) oxidase is a common and essential biosynthetic enzyme for butenolide-type
Streptomyces
hormones. Moreover, the diffusible butenolide compounds from a donor
Streptomyces
strain were recognized by the recipient
Streptomyces
strain of a different species, resulting in the initiation of secondary metabolism in the recipient. This is an interesting report on the chemical interaction between two different streptomycetes via
Streptomyces
hormones. Information on the metabolite network may provide useful hints not only to clarification of the regulatory mechanism of secondary metabolism, but also to understanding of the chemical communication among streptomycetes to control their physiological traits.
Type IV Pili Promote Clostridium difficile Adherence and Persistence in a Mouse Model of Infection
Authors: McKee Robert W. , Aleksanyan Naira , Garrett Elizabeth M. , Tamayo Rita
Published: February 2018

Cyclic diguanylate (c-di-GMP) is a second messenger that regulates the transition from motile to sessile lifestyles in numerous bacteria and controls virulence factor production in a variety of pathogens. In
Clostridium difficile
, c-di-GMP negatively regulates flagellum biosynthesis and swimming motility and promotes the production of type IV pili (TFP), biofilm formation, and surface motility
in vitro
. Flagella have been identified as colonization factors in
C. difficile
, but the role of TFP in adherence to host cells and in colonization of the mammalian gut is unknown. Here we show that c-di-GMP promotes adherence to epithelial cells
in vitro
, which can be partly attributed to the loss of flagella. Using TFP-null mutants, we demonstrate that adherence to epithelial cells is partially mediated by TFP and that this TFP-mediated adherence requires c-di-GMP regulation. In a mouse model of colonization, the TFP-null mutants initially colonized the intestine as well as the parental strain but were cleared more quickly. Moreover, compared to the parent strain,
C. difficile
strains lacking TFP were particularly deficient in association with the cecal mucosa. Together these data indicate that TFP and their positive regulation by c-di-GMP promote attachment of
C. difficile
to the intestinal epithelium and contribute to persistence of
C. difficile
in the host intestine.
PhdA Catalyzes the First Step of Phenazine-1-Carboxylic Acid Degradation in Mycobacterium fortuitum
Authors: Costa Kyle C. , Moskatel Leon S. , Meirelles Lucas A. , Newman Dianne K.
Published: February 2018

Phenazines are a class of bacterially produced redox-active metabolites that are found in natural, industrial, and clinical environments. In
Pseudomonas
spp., phenazine-1-carboxylic acid (PCA)—the precursor of all phenazine metabolites—facilitates nutrient acquisition, biofilm formation, and competition with other organisms. While the removal of phenazines negatively impacts these activities, little is known about the genes or enzymes responsible for phenazine degradation by other organisms. Here, we report that the first step of PCA degradation by
Mycobacterium fortuitum
is catalyzed by a
ph
enazine-
d
egrading decarboxylase (PhdA). PhdA is related to members of the UbiD protein family that rely on a prenylated flavin mononucleotide cofactor for activity. The gene for PhdB, the enzyme responsible for cofactor synthesis, is present in a putative operon with the gene encoding PhdA in a region of the
M. fortuitum
genome that is essential for PCA degradation. PhdA and PhdB are present in all known PCA-degrading organisms from the
Actinobacteria
.
M. fortuitum
can also catabolize other
Pseudomonas
-derived phenazines such as phenazine-1-carboxamide, 1-hydroxyphenazine, and pyocyanin. On the basis of our previous work and the current characterization of PhdA, we propose that degradation converges on a common intermediate: dihydroxyphenazine. An understanding of the genes responsible for degradation will enable targeted studies of phenazine degraders in diverse environments.

IMPORTANCE
Bacteria from phylogenetically diverse groups secrete redox-active metabolites that provide a fitness advantage for their producers. For example, phenazines from
Pseudomonas
spp. benefit the producers by facilitating anoxic survival and biofilm formation and additionally inhibit competitors by serving as antimicrobials. Phenazine-producing pseudomonads act as biocontrol agents by leveraging these antibiotic properties to inhibit plant pests. Despite this importance, the fate of phenazines in the environment is poorly understood. Here, we characterize an enzyme from
Mycobacterium fortuitum
that catalyzes the first step of phenazine-1-carboxylic acid degradation. Knowledge of the genetic basis of phenazine degradation will facilitate the identification of environments where this activity influences the microbial community structure.