bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractHypoxia 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

AbstractMast 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

AbstractThis 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.
A spatial‐knowledge‐enhanced heuristic for solving the p‐median problem
Authors: Mu Wangshu , Tong Daoqin 
Published: February 2018

AbstractThe 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

AbstractUnderstanding 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

AbstractObjectiveTo assess the impact of a simulated CO2 pneumoperitoneum environment on the viability and proliferation of canine transitional cell carcinoma (TCC) cells in vitro.Study designIn vitro study.MethodsA 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.ResultsThe 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.
The dual‐gate model for pentameric ligand‐gated ion channels activation and desensitization
Authors: Gielen Marc , Corringer Pierre‐Jean 
Published: February 2018

AbstractPentameric 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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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.
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

ABSTRACT

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

ABSTRACT

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

ABSTRACT

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

ABSTRACT

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.
Identification of Piperazinylbenzenesulfonamides as New Inhibitors of Claudin-1 Trafficking and Hepatitis C Virus Entry
Authors: Riva Laura , Song Ok-ryul , Prentoe Jannick , Helle François , L'homme Laurent , Gattolliat Charles-Henry , Vandeputte Alexandre , Fénéant Lucie , Belouzard Sandrine , Baumert Thomas F. , Asselah Tarik , Bukh Jens , Brodin Priscille , Cocquerel Laurence , Rouillé Yves , Dubuisson Jean 
Published: February 2018

ABSTRACTHepatitis C virus (HCV) infection causes 500,000 deaths annually, in association with end-stage liver diseases. Investigations of the HCV life cycle have widened the knowledge of virology, and here we discovered that two piperazinylbenzenesulfonamides inhibit HCV entry into liver cells. The entry of HCV into host cells is a complex process that is not fully understood but is characterized by multiple spatially and temporally regulated steps involving several known host factors. Through a high-content virus infection screening analysis with a library of 1,120 biologically active chemical compounds, we identified SB258585, an antagonist of serotonin receptor 6 (5-HT6), as a new inhibitor of HCV entry in liver-derived cell lines as well as primary hepatocytes. A functional characterization suggested a role for this compound and the compound SB399885, which share similar structures, as inhibitors of a late HCV entry step, modulating the localization of the coreceptor tight junction protein claudin-1 (CLDN1) in a 5-HT6-independent manner. Both chemical compounds induced an intracellular accumulation of CLDN1, reflecting export impairment. This regulation correlated with the modulation of protein kinase A (PKA) activity. The PKA inhibitor H89 fully reproduced these phenotypes. Furthermore, PKA activation resulted in increased CLDN1 accumulation at the cell surface. Interestingly, an increase of CLDN1 recycling did not correlate with an increased interaction with CD81 or HCV entry. These findings reinforce the hypothesis of a common pathway, shared by several viruses, which involves G-protein-coupled receptor-dependent signaling in late steps of viral entry.IMPORTANCEThe HCV entry process is highly complex, and important details of this structured event are poorly understood. By screening a library of biologically active chemical compounds, we identified two piperazinylbenzenesulfonamides as inhibitors of HCV entry. The mechanism of inhibition was not through the previously described activity of these inhibitors as antagonists of serotonin receptor 6 but instead through modulation of PKA activity in a 5-HT6-independent manner, as proven by the lack of 5-HT6 in the liver. We thus highlighted the involvement of the PKA pathway in modulating HCV entry at a postbinding step and in the recycling of the tight junction protein claudin-1 (CLDN1) toward the cell surface. Our work underscores once more the complexity of HCV entry steps and suggests a role for the PKA pathway as a regulator of CLDN1 recycling, with impacts on both cell biology and virology.