bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of indoor air quality of day care centers in children with different predisposition for asthma
Authors: Carreiro‐Martins Pedro , Papoila Ana Luisa , Caires Iolanda , Azevedo Susana , Cano Maria Manuela , Virella Daniel , Leiria‐Pinto Paula , Teixeira João Paulo , Rosado‐Pinto José , Annesi‐Maesano Isabella , Neuparth Nuno
Published: December 2015

Background

Scarce information is available about the relationships between indoor air quality (IAQ) at day care centers (DCC), the estimated predisposition for asthma, and the actual wheezing susceptibility.

Methods

In the Phase II of ENVIRH study, 19 DCC were recruited after cluster analysis. Children were evaluated firstly using the ISAAC questionnaire and later by a follow‐up questionnaire about recent wheezing. A positive asthma predictive index (API) was considered as predisposition for asthma. Every DCC was audited for IAQ and monitored for chemical and biologic contaminants.

Results

We included 1191 children, with a median age of 43 (P25–P75: 25–58) months. Considering the overall sample, in the first questionnaire, associations were found between CO2 concentration (increments of 200 ppm) and diagnosis of asthma (OR: 1.10; 95% CI: 1.00–1.20). Each increment of 100 μg/m3 of total volatile organic compounds (TVOC) and 1 μg of Der p1/g of dust were associated with wheezing in the previous 12 months (OR: 1.06; 95% CI: 1.01–1.11 and OR: 1.06; 95% CI: 0.99–1.12, respectively). In the follow‐up questionnaire, TVOC were again associated with wheezing (OR: 1.05; 95% CI: 1.00–1.11). Children exposed to fungal concentration above the 75th percentile had also higher odds of wheezing at follow‐up. TVOC were associated with wheezing in children with either negative or positive API.

Conclusions

IAQ in DCC seems to be associated with wheezing, in children with and without predisposition for asthma.
Alterations in the gut microbiotas of children with food sensitization in early life
Authors: Chen Chien‐Chang , Chen Kun‐Jei , Kong Man‐Shan , Chang Hung‐Ju , Huang Jing‐Long
Published: December 2015

Background

We hypothesized that food sensitization (FS) in children could be linked to specific gut microbiota. The aim of our study is to quantify and evaluate differences in gut microbiota composition between children with FS and healthy controls.

Methods

A case–control study of 23 children with FS and 22 healthy children was performed. Individual microbial diversity and composition were analyzed via parallel barcoded 454 pyrosequencing targeting the 16S rRNA gene hypervariable V3–V5 regions.

Results

The children with FS exhibited lower diversity of both the total microbiota (p = 0.01) and the bacterial phylum Bacteroidetes (p = 0.02). In these children, the number of Bacteroidetes bacteria was significantly decreased and that of Firmicutes were significantly increased compared with the healthy children. At the genus level, we observed significant increases in the numbers of Sphingomonas, Sutterella, Bifidobacterium, Collinsella, Clostridium sensu stricto, Clostridium IV, Enterococcus, Lactobacillus, Roseburia, Faecalibacterium, Ruminococcus, Subdoligranulum, and Akkermansia in the FS group. We also found significant decreases in the numbers of Bacteroides, Parabacteroides, Prevotella, Alistipes, Streptococcus, and Veillonella in this group. Furthermore, linear discriminant analysis (LDA) coupled with effect size measurements revealed the most differentially abundant taxa (increased abundances of Clostridium IV and Subdoligranulum and decreased abundances of Bacteroides and Veillonella), which could be used to identify FS.

Conclusions

Our results showed that FS is associated with compositional changes in the gut microbiota. These findings could be useful for developing strategies to control the development of FS or atopy by modifying the gut microbiota.
Development and validation of asthma questionnaire for assessing and achieving best control in preschool‐age children
Authors: Sato Kazuki , Sato Yasunori , Nagao Mizuho , Shimojo Naoki , Yoshihara Shigemi , Adachi Yuichi , Kameda Makoto , Terada Akihiko , Fujisawa Takao
Published: December 2015

Background

Several patient‐/caregiver‐completed questionnaires have been utilized for the assessment of asthma control. However, due to the diversity in medical/social circumstances, they may not be optimal for use in all countries. The Japanese pediatric asthma guideline (JPGL) aims at higher levels of control compared with other international guidelines, based on a strong social demand for best care. We developed a new control test to help meet that demand.

Methods

A 34‐item working questionnaire was developed based on input from pediatric asthma specialists and the caregivers of preschool children with asthma. The questionnaire was administered to caregivers of 565 patients aged <6 years who had physician‐diagnosed asthma or β2‐agonist‐responsive recurrent wheeze. Then, 6 questions for assessing JPGL‐defined control levels were selected from the 34 questions by stepwise logistic regression methods using randomly selected questionnaires completed by two‐thirds of the caregivers. We named that set of questions the Best Asthma Control Test for Preschoolers (Best ACT‐P). Validation of Best ACT‐P was performed using the remaining completed questionnaires.

Results

The 6 questions asked about the frequency/severity of cold‐induced wheeze, nighttime awakening, exercise‐induced symptoms, and disruption of family life due to asthma in the past 4 weeks and hospitalization in the past 12 months. The 6‐item logistic model showed good statistical fit, and the scores for the physicians' ratings of the asthma control differed significantly in the hypothetical direction.

Conclusions

Best ACT‐P is a valid caregiver‐completed questionnaire of asthma control in preschoolers in whom total control needs to be achieved.
Allergen immunotherapy for the prevention of allergic disease: protocol for a systematic review
Authors: Dhami Sangeeta , Nurmatov Ulugbek , Halken Susanne , Calderón Moises A. , Muraro Antonella , Roberts Graham , Toit George Du , Kleine‐Tebbe Jörg , Larenas‐Linnemann Desiree , Lau Susanne , Matricardi Paolo Maria , Pajno Giovanni , Papadopoulos Nikolaos G. , Pfaar Oliver , Ryan Dermot , Santos Alexandra F. , Timmermanns Frans , Wahn Ulrich , Sheikh Aziz
Published: December 2015

Background

The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for the Prevention of Allergic Disease. We seek to critically assess the effectiveness, cost‐effectiveness, and safety of AIT in the prevention of allergic disease.

Methods

We will undertake a systematic review, which will involve searching international biomedical databases for published, in progress and unpublished evidence. Studies will be independently screened against pre‐defined eligibility criteria and critically appraised using established instruments. Data will be descriptively and, if possible and appropriate, quantitatively synthesized.

Discussion

The findings from this review will be used to inform the development of recommendations for EAACI's Guidelines on AIT.
Interrelated responses of tomato plants and the leaf minerTuta absolutato nitrogen supply
Authors: Larbat R. , Adamowicz S. , Robin C. , Han P. , Desneux N. , Le Bot J.
Published: December 2015

Plant–insect interactions are strongly modified by environmental factors. This study evaluates the influence of nitrogen fertilisation on the tomato (Solanum lycopersicumL.) cv. Santa clara and the leafminer (Tuta absoluta(Meyrick), Lepidoptera: Gelechiidae). Greenhouse‐grown tomato plants were fed hydroponically on a complete nutrient solution containing either a high nitrogen concentration (HN) sustaining maximum growth or a low nitrogen concentration (LN) limiting plant growth. Insect‐free plants were compared with plants attacked byT. absoluta. Seven and 14 days after artificial oviposition leading to efficacious hatching and larvae development, we measured total carbon, nitrogen and soluble protein as well as defence compounds (phenolics, glycoalkaloids, polyphenol oxidase activity) in theHNversusLNplants. Only in theHNtreatment didT. absolutainfestation slightly impair leaf growth and induce polyphenol oxidase (PPO) activity in the foliage. Neither the concentration of phenolic compounds and proteins nor the distribution of nitrogen within the plant was affected byT. absolutainfestation. In contrast,LNnutrition impairedT. absoluta‐inducedPPOactivity. It decreased protein and total nitrogen concentration of plant organs and enhanced the accumulation of constitutive phenolics and tomatine. Moreover,LNnutrition impairedT. absolutadevelopment by notably decreasing pupal weight and lengthening the development period from egg to adult. Adjusting the level of nitrogen nutrition may thus be a means of altering the life cycle ofT. absoluta. This study provides a comprehensive dataset concerning interrelated responses of tomato plants andT. absolutato nitrogen nutrition.
Tan spot of pyrethrum is caused by a Didymella species complex
Authors: Pearce T. L. , Scott J. B. , Crous P. W. , Pethybridge S. J. , Hay F. S.
Published: December 2015

Tan spot is a disease of pyrethrum (Tanacetum cinerariifolium) in Australia. Recent increases in the severity and incidence of the disease have prompted a re‐evaluation of the pathogen, originally described as Microsphaeropsis tanaceti, including its phylogenetic relationships and morphology. Nucleotide comparison of partial sequences of the nuclear ribosomal internal transcribed spacer, β‐tubulin, large subunit 28S nrDNA (LSU), actin and glyceraldehyde‐3‐phosphate dehydrogenase loci identified two distinct haplotypes within the species. Haplotype differentiation was consistent for each locus, except for the LSU, within which sequences were identical across all isolates. Morphological variation, especially culture pigmentation and conidial size, consistently supported the phylogenetic data distinguishing two haplotypes. Phylogenetic comparisons of M. tanaceti incorporating 98 Didymellaceae species did not associate the M. tanaceti haplotypes with the genus Microsphaeropsis. The two M. tanaceti haplotypes were closely related, and clustered in the Didymella sensu stricto clade. Based on these phylogenetic results, supported by their distinct morphology and cultural characteristics, the two haplotypes of M. tanaceti are reclassified as two species of Didymella, namely D. rosea and D. tanaceti. The implications of two closely related species causing tan spot of pyrethrum are discussed.
Profile of Penicillium species in the pear supply chain
Authors: Scholtz I. , Korsten L.
Published: December 2015

Postharvest fruit decay caused by Penicillium pathogens is considered to be one of the most important challenges in the pear industry resulting in market‐end losses. Moving export fruit through different environments exposes the product to extensive handling, temperature variations and microbes. Therefore, the profile of Penicillium spp. present in the pear export chain from South Africa (SA) to the UK was studied over a four‐year period. Sampling was done at two packhouse facilities, controlled atmosphere and cold storage areas in SA and at two repack facilities and cold storages as well as a distribution centre and a retailer in the UK. Sampling consisted of swabbing walls and floors and using active and passive air sampling. In total, 5056 isolates were obtained, purified and grouped into 282 morphological groups. Of these, 350 representative isolates were selected for further identification. The five most dominant species in the pear chain were: P. glabrum (23·40%), P. chrysogenum (15·13%), P. crustosum (14·16%), P. brevicompactum (8·96%) and P. expansum (8·39%), of which the latter three were confirmed pathogenic on pears. This study provides a framework to monitor the inoculum potential in environments that fruit move through while being exported.
The impact of resistant and susceptible wheat cultivars on the multiplication of Heterodera filipjevi and H. avenae in parasite‐infested soil
Authors: Cui L. , Sun L. , Gao X. , Song W. , Wang X. M. , Li H. L. , Liu Z. Y. , Tang W. H. , Li H. J.
Published: December 2015

Cereal cyst nematode (CCN) severely threatens wheat production in many regions of China. Cultivars susceptible to CCN are the main reason for its spread. This study was initiated to determine whether wheat cultivars conferring different resistance levels are the dominant determinants of CCN populations in the rhizospheric soil. Field experiments were conducted at two locations in Henan province, China, where high populations of Heterodera filipjevi or H. avenae have occurred, during the growing seasons of 2010/11 and 2011/12. Conventional enumeration of white female nematodes on the plant roots, reproductive factor (Rf) and a molecular diagnostic approach, PreDicta B test, a soil testing service based on a sensitive quantitative PCR technique, were used to determine the nematode populations in the rhizospheric soils of seven common wheat and durum wheat cultivars with different reactions to CCN. The resistant responses to CCN conferred by durum wheat Wascana and Wakooma and common wheat Madsen were effective against both H. filipjevi and H. avenae and resulted in significantly fewer nematodes (<5 females) on the roots, and lower Rf. Those cultivars were effective in limiting nematode propagation, resulting in fewer CCN eggs in their rhizospheric soils. Taikong 6 conferred moderate resistance (5–10 females) to both Heterodera species. Tianmin 668 only showed resistance to H. avenae. Aikang 58 and Wenmai 19 were susceptible to both CCN species, which facilitated increases in the nematode populations. These results demonstrate that the reactions to CCN of wheat genotypes have obvious impact on the propagation of nematodes.
Salamander diversity of reforested abandoned surface coal mines in the Appalachian Region, U.S.A.
Authors: Brady Joseph K.
Published: December 2015

Surface coal mining is a pervasive form of land use and leading cause of deforestation in the Appalachian Region of the United States. Contemporary reclamation practices tend to produce strongly altered landscapes that inhibit forest succession, so there is a need for the development of alternative methods. Surface coal mines that preceded modern reclamation laws, known as abandoned mine lands, have become reforested in many locations and may serve as a model for improving the restoration of forests in postmining landscapes. I compared salamander diversity between 5 forests growing atop abandoned surface coal mines to 5 similar aged reference forests in southeastern Ohio using time constrained transect searches in autumn 2012 and spring 2013. The survey revealed 1,480 salamander individuals, representing 11 different species from 3 different families. The vast majority of salamanders (93%) were from the family Plethodontidae. Salamander species richness was significantly higher in reference forests than in mined forests, but this difference was contingent on the presence of stream‐dependent species in the reference forests. Salamander relative abundance was not significantly different between reference and mined forests. This survey demonstrates that reforested abandoned surface coal mines can provide suitable habitat for many forest‐dependent, terrestrial salamander species, but impaired water quality of headwater streams may limit the colonization of these forests by stream‐dependent species.
The alluvial architecture of a suspended sediment dominated meandering river: the Río Bermejo, Argentina
Authors: Sambrook Smith Gregory H. , Best James L. , Leroy Jessica Z. , Orfeo Oscar
Published: December 2015

The alluvial architecture of fine‐grained (silt‐bed) meandering rivers remains poorly understood in comparison to the extensive study given to sand‐bed and gravel‐bed channels. This paucity of knowledge stems, in part, from the difficulty of studying such modern rivers and deriving analogue information from which to inform facies models for ancient sediments. This paper employs a new technique, the parametric echosounder, to quantify the subsurface structure of the Río Bermejo, Argentina, which is a predominantly silt‐bed river with a large suspended sediment load. These results show that the parametric echosounder can provide high‐resolution (decimetre) subsurface imaging from fine‐grained rivers that is equivalent to the more commonly used ground‐penetrating radar that has been shown to work well in coarser‐grained rivers. Analysis of the data reveals that the alluvial architecture of the Río Bermejo is characterized by large‐scale inclined heterolithic stratification generated by point‐bar evolution, and associated large‐scale scour surfaces that result from channel migration. The small‐scale and medium‐scale structure of the sedimentary architecture is generated by vertical accretion deposits, bed sets associated with small bars, dunes and climbing ripples and the cut and fill from small cross‐bar channels. This style of alluvial architecture is very different from other modern fine‐grained rivers reported in the literature that emphasize the presence of oblique accretion. The Río Bermejo differs from these other rivers because it is much more active, with very high rates of bank erosion and channel migration. Modern examples of this type of highly active fine‐grained river have been reported rarely in the literature, although ancient examples are more prevalent and show similarities with the alluvial architecture of the Río Bermejo, which thus represents a useful analogue for their identification and interpretation. Although the full spectrum of the sedimentology of fine‐grained rivers has yet to be revealed, meandering rivers dominated by lateral or oblique accretion probably represent end members of such channels, with the specific style of sedimentation being controlled by grain size and sediment load characteristics.
Porosity and size gradation of saturated gravel with percolated fines
Authors: Núñez‐González Francisco , Martín‐Vide Juan Pedro , Kleinhans Maarten G.
Published: December 2015

Fine particles may infiltrate through coarse alluvial beds and eventually saturate the subsurface pore space. It is essential to understand the conditions that lead to bed saturation, and to forecast the packing characteristics of saturated beds to assess the effect of excess fine sediment supply on a number of processes that occur in the stream–sediment boundary. To address this problem, in this study, a new method is introduced to predict the grain‐size distribution for the saturated condition, and the resulting porosity decrease, given the characteristics of the bed and the supplied sediments. The new method consists of the numerical aggregation of infilling fines in a finite bed volume, during which the bed properties change to affect further infilling. An existing semi‐empirical, particle packing model is implemented to identify these properties. It is shown that these types of models are adequate to describe regimes of natural sediment fabric quantitatively, and are thus useful tools in the analysis of sediment infiltration processes. Unlike previous developments to quantify saturated bed conditions, which assume that the supplied material is uniform and finer than the bed pore openings, the method developed herein considers poorly sorted fines, and can identify size fractions that are able to ingress into the bed due to being smaller than the particles that form the bed structure. Application of the new method to published experimental data showed that the final content of infiltrated fines is strongly sensitive to the initial bed packing density, highlighting the need to measure and understand open‐work gravel deposits. In addition, the new method was shown to be suitable for assessing the degree of bed saturation, when it was applied to a published data set of field samples.
Delayed Valuation: A Reanalysis of Goal Features, “Upward” Complementizer Agreement, and the Mechanics of Case
Authors: Carstens Vicki
Published: December 2015

There are at least four opposing views on the directionality and configuration of Agree relations. In mainstream minimalism, Agree is strictly downward “probing” (Chomsky,; Bošković; Epstein & Seely), but some recent works argue that Agree always looks upward (Zeijlstra, Wurmbrand). A third perspective takes agreement to follow from the Spec–head configuration (Koopman), and under a fourth proposal, the directionality of Agree varies parametrically (Baker). Although each approach has some empirical support, none achieves the strict conceptual necessity that is a central goal of minimalist theory. I argue, following Epstein's () approach to c‐command, that a downward directionality for Agree follows automatically and necessarily from the bottom‐to‐top construction of syntactic objects. But if auFdoes not find any source of valuation in its c‐command domain at first Merge, directionality‐free matching anddelayed valuationare possible up to the point of cyclic Transfer. The approach eliminates several stipulations from agreement theory, deducing that theuFs making goals “active” in Agree relations are simply those that find no match in their c‐command domains at Merge.
Spatiotemporal Resolution of Rab9 and CI‐MPR Dynamics in the Endocytic Pathway
Authors: Kucera Ana , Borg Distefano Marita , Berg‐Larsen Axel , Skjeldal Frode , Repnik Urska , Bakke Oddmund , Progida Cinzia
Published: December 2015

Rab9 is a small GTPase that localizes to the trans‐Golgi Network (TGN) and late endosomes. Its main function has long been connected to the recycling of mannose‐6‐phosphate receptors (MPRs). However, recent studies link Rab9 also to autophagy and lysosome biogenesis. In this paper, using confocal imaging, we characterize for the first time the live dynamics of the Rab9 constitutively active mutant, Rab9Q66L. We find that it localizes predominantly to late endosomes and that its expression in HeLa cells disperses TGN46 and cation‐independent (CI‐MPR) away from the Golgi yet, has no effect on the retrograde transport of CI‐MPR. We also show that CI‐MPR and Rab9 enter the endosomal pathway together at the transition stage between early, Rab5‐positive, and late, Rab7a‐positive, endosomes. CI‐MPR localizes transiently to separate domains on these endosomes, where vesicles carrying CI‐MPR attach and detach within seconds. Taken together, our results demonstrate that Rab9 mediates the delivery of CI‐MPR to the endosomal pathway, entering the maturing endosome at the early‐to‐late transition.
Human bone marrow processing using a new continuous‐flow cell separation device
Authors: Guttridge Martin G. , Bailey Christopher , Sidders Christopher , Nichols Jennifer , Bromham Jane , Watt Suzanne M.
Published: December 2015

BACKGROUND

Processing of bone marrow (BM) is often required to remove incompatible red blood cells (RBCs) or to reduce the volume before transplantation or cryopreservation. We have evaluated the Spectra Optia apheresis system to determine its effectiveness in volume reduction and RBC depletion of human BM before transplantation.

STUDY DESIGN AND METHODS

BM from 30 donations (28 allogeneic and two autologous) were processed using the Spectra Optia over a 12‐month period. The mean BM collection volume was 1094 ± 337 mL and RBC volume was 374 ± 148 mL. Processing using the Spectra Optia was as described by the manufacturer.

RESULTS

Volume reduction achieved was 93.0 ± 1.2%; RBC depletion was 98.8 ± 0.4%; and mononuclear, CD34+, and CD3+ cell recoveries were 79.12 ± 14.03, 88.36 ± 13.76, and 79.84 ± 16.27%, respectively. In total 26 of 28 processed allografts were transplanted; 24 achieved neutrophil engraftment in 20.7 ± 5.9 days and 18 achieved platelet engraftment in 19.6 ± 8.9 days. Time in transit significantly affected the Spectra Optia's ability to recover mononuclear, CD34+, and CD3+ cells, and the overall age of the BM at the time of processing significantly affected the recovery of mononuclear and CD3+ cells, but not CD34+ cells. Time in storage at 2 to 6°C had no adverse effect on processing.

CONCLUSION

This study demonstrates that the Spectra Optia can effectively volume reduce and RBC deplete human BM before transplantation. Time in transit should be as short as possible but may be extended up to 24 hours if the donation is refrigerated during transit.
Metabolomics in transfusion medicine
Authors: Nemkov Travis , Hansen Kirk C. , Dumont Larry J. , D'Alessandro Angelo
Published: December 2015

Biochemical investigations on the regulatory mechanisms of red blood cell (RBC) and platelet (PLT) metabolism have fostered a century of advances in the field of transfusion medicine. Owing to these advances, storage of RBCs and PLT concentrates has become a lifesaving practice in clinical and military settings. There, however, remains room for improvement, especially with regard to the introduction of novel storage and/or rejuvenation solutions, alternative cell processing strategies (e.g., pathogen inactivation technologies), and quality testing (e.g., evaluation of novel containers with alternative plasticizers). Recent advancements in mass spectrometry–based metabolomics and systems biology, the bioinformatics integration of omics data, promise to speed up the design and testing of innovative storage strategies developed to improve the quality, safety, and effectiveness of blood products.

Here we review the currently available metabolomics technologies and briefly describe the routine workflow for transfusion medicine–relevant studies. The goal is to provide transfusion medicine experts with adequate tools to navigate through the otherwise overwhelming amount of metabolomics data burgeoning in the field during the past few years.

Descriptive metabolomics data have represented the first step omics researchers have taken into the field of transfusion medicine. However, to up the ante, clinical and omics experts will need to merge their expertise to investigate correlative and mechanistic relationships among metabolic variables and transfusion‐relevant variables, such as 24‐hour in vivo recovery for transfused RBCs. Integration with systems biology models will potentially allow for in silico prediction of metabolic phenotypes, thus streamlining the design and testing of alternative storage strategies and/or solutions.
Combined Energy and Process Simulation to Foster Efficiency in Non-automated Material Handling System Design
Authors: Fekete Patrick , Lim Sirirat , Martin Steve , Kuhn Katja , Wright Nick
Published: December 2015

Energy and resource efficiency are becoming more and more important objectives in industrial companies, so that it has also become relevant to material handling as part of the lean strategy in supply chain management. The design of sustainable, energy efficient material handling systems and processes depends on methods and tools that analyse and evaluate the composition of the technologies and processes of the system. Therefore analysis on detailed data on energy consumption, energy supply and process organisation is required to improve overall system efficiency. This study proposes a novel approach to energy data generation based on Standardised Energy Consuming Activities (SECA). Simulating process energy consumption and consumption behaviour based on process function investigations increases knowledge about the sequence and characteristics of energy consumption and its process allocation. Executing the research project Usable Battery Energy of the material handling equipment was identified to be gradable by 25% to 43% in order to increase equipment availability and thus system efficiency. In the performed case study a system range extension of 19% to 33% was reached by the implementation of a fast engaging charging system using process related idle times. Generally applicable data is required for the design of a scalable simulation to enable the identification of requirements to the design of non-automated material handling system components. The proposed framework forms the basis necessary for the derivation and evaluation of technical and organisational improvement of system efficiency with respect to energy, ecological and economic objectives.
Endothelin regulates intermittent hypoxia‐induced lipolytic remodelling of adipose tissue and phosphorylation of hormone‐sensitive lipase
Authors: Briançon‐Marjollet Anne , Monneret Denis , Henri Marion , Hazane‐Puch Florence , Pepin Jean‐Louis , Faure Patrice , Godin‐Ribuot Diane
Published: December 2015

Key points

Endothelin‐1 (ET‐1) is upregulated upon intermittent hypoxia and has lipolytic effects.

Intermittent hypoxia induces adipose tissue lipolysis that may be mediated by ET‐1.

In the present study, we show that ET‐1 is involved in adipose tissue remodelling induced by intermittent hypoxia and that phosphorylation of hormone‐sensitive lipase could be one mechanism mediating this effect.

We also show that ET‐1 upregulates its own and its type A endothelin receptor expression, possibly leading to an autoactivatory loop.

These results help us better understand the mechanisms of dyslipidaemia in disorders associated with intermittent hypoxia, such as obstructive sleep apnoea.

Obstructive sleep apnoea syndrome is characterized by repetitive episodes of upper airway collapse during sleep resulting in chronic intermittent hypoxia (IH). Obstructive sleep apnoea syndrome, through IH, promotes cardiovascular and metabolic disorders. Endothelin‐1 (ET‐1) secretion is upregulated by IH, and is able to modulate adipocyte metabolism. Therefore, the present study aimed to characterize the role of ET‐1 in the metabolic consequences of IH on adipose tissue in vivo and in vitro. Wistar rats were submitted to 14 days of IH‐cycles (30 s of 21% FiO2 and 30 s of 5% FiO2; 8 h day−1) or normoxia (air–air cycles) and were treated or not with bosentan, a dual type A and B endothelin receptor (ETA‐R and ETB‐R) antagonist. Bosentan treatment decreased plasma free fatty acid and triglyceride levels, and inhibited IH‐induced lipolysis in adipose tissue. Moreover, IH induced a 2‐fold increase in ET‐1 transcription and ETA‐R expression in adipose tissue that was reversed by bosentan. In 3T3‐L1 adipocytes, ET‐1 upregulated its own and its ETA‐R transcription and this effect was abolished by bosentan. Moreover, ET‐1 induced glycerol release and inhibited insulin‐induced glucose uptake. Bosentan and BQ123 inhibited these effects. Bosentan also reversed the ET‐1‐induced phosphorylation of hormone‐sensitive lipase (HSL) on Ser660. Finally, ET‐1‐induced lipolysis and HSL phosphorylation were also observed under hypoxia. Altogether, these data suggest that ET‐1 is involved in IH‐induced lipolysis in Wistar rats, and that upregulation of ET‐1 production and ETA‐R expression by ET‐1 itself under IH could amplify its effects. Moreover, ET‐1‐induced lipolysis could be mediated through ETA‐R and activation of HSL by Ser660 phosphorylation.
Increasing taurine intake and taurine synthesis improves skeletal muscle function in the mdx mouse model for Duchenne muscular dystrophy
Authors: Terrill Jessica R. , Pinniger Gavin J. , Graves Jamie A. , Grounds Miranda D. , Arthur Peter G.
Published: December 2015

Key points

Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease associated with increased inflammation, oxidative stress and myofibre necrosis.

Cysteine precursor antioxidants such as N‐acetyl cysteine (NAC) and l‐2‐oxothiazolidine‐4‐carboxylate (OTC) reduce dystropathology in the mdx mouse model for DMD, and we propose this is via increased synthesis of the amino acid taurine.

We compared the capacity of OTC and taurine treatment to increase taurine content of mdx muscle, as well as effects on in vivo and ex vivo muscle function, inflammation and oxidative stress.

Both treatments increased taurine in muscles, and improved many aspects of muscle function and reduced inflammation. Taurine treatment also reduced protein thiol oxidation and was overall more effective, as OTC treatment reduced body and muscle weight, suggesting some adverse effects of this drug.

These data suggest that increasing dietary taurine is a better candidate for a therapeutic intervention for DMD.

Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease for which there is no widely available cure. Whilst the mechanism of loss of muscle function in DMD and the mdx mouse model are not fully understood, disruptions in intracellular calcium homeostasis, inflammation and oxidative stress are implicated. We have shown that protein thiol oxidation is increased in mdx muscle, and that the indirect thiol antioxidant l‐2‐oxothiazolidine‐4‐carboxylate (OTC), which increases cysteine availability, decreases pathology and increases in vivo strength. We propose that the protective effects of OTC are a consequence of conversion of cysteine to taurine, which has itself been shown to be beneficial to mdx pathology. This study compares the efficacy of taurine with OTC in decreasing dystropathology in mdx mice by measuring in vivo and ex vivo contractile function and measurements of inflammation and protein thiol oxidation. Increasing the taurine content of mdx muscle improved both in vivo and ex vivo muscle strength and function, potentially via anti‐inflammatory and antioxidant effects of taurine. OTC treatment increased taurine synthesis in the liver and taurine content of mdx muscle, improved muscle function and decreased inflammation. However, OTC was less effective than taurine treatment, with OTC also decreasing body and EDL muscle weights, suggesting that OTC had some detrimental effects. These data support continued research into the use of taurine as a therapeutic intervention for DMD, and suggest that increasing dietary taurine is the better strategy for increasing taurine content and decreasing severity of dystropathology.
Microglia modulate brainstem serotonergic expression following neonatal sustained hypoxia exposure: implications for sudden infant death syndrome
Authors: MacFarlane P. M. , Mayer C. A. , Litvin D. G.
Published: December 2015

Key points

Neonatal sustained hypoxia exposure modifies brainstem microglia and serotonin expression.

The altered brainstem neurochemistry is associated with impaired ventilatory responses to acute hypoxia and mortality.

The deleterious effects of sustained hypoxia exposure can be prevented by an inhibitor of activated microglia.

These observations demonstrate a potential cause of the brainstem serotonin abnormalities thought to be involved in sudden infant death syndrome.

We showed previously that the end of the second postnatal week (days P11–15) represents a period of development during which the respiratory neural control system exhibits a heightened vulnerability to sustained hypoxia (SH, 11% O2, 5 days) exposure. In the current study, we investigated whether the vulnerability to SH during the same developmental time period is associated with changes in brainstem serotonin (5‐HT) expression and whether it can be prevented by the microglia inhibitor minocycline. Using whole‐body plethysmography, SH attenuated the acute (5 min) hypoxic ventilatory response (HVR) and caused a high incidence of mortality compared to normoxia rats. SH also increased microglia cell numbers and decreased 5‐HT immunoreactivity in the nucleus of the solitary tract (nTS) and dorsal motor nucleus of the vagus (DMNV). The attenuated HVR, mortality, and changes in nTS and DMNV immunoreactivity was prevented by minocycline (25 mg kg−1/2 days during SH). These data demonstrate that the 5‐HT abnormalities in distinct respiratory neural control regions can be initiated by prolonged hypoxia exposure and may be modulated by microglia activity. These observations share several commonalities with the risk factors thought to underlie the aetiology of sudden infant death syndrome, including: (1) a vulnerable neonate; (2) a critical period of development; (3) evidence of hypoxia; (4) brainstem gliosis (particularly the nTS and DMNV); and (5) 5‐HT abnormalities.
Enzymatically active biomimetic micropropellers for the penetration of mucin gels
Authors: Walker Debora , Käsdorf Benjamin T. , Jeong Hyeon-Ho , Lieleg Oliver , Fischer Peer
Published: December 2015

Magnetic microparticles decorated with enzymes can penetrate mucin, which is a barrier for most particle-based drug carriers.
Reconciling past changes in Earth’s rotation with 20th century global sea-level rise: Resolving Munk’s enigma
Authors: Mitrovica Jerry X. , Hay Carling C. , Morrow Eric , Kopp Robert E. , Dumberry Mathieu , Stanley Sabine
Published: December 2015

Reanalysis of Earth rotation observations reconciles them with globally averaged sea-level change in the 20th century.
A new time tree reveals Earth history’s imprint on the evolution of modern birds
Authors: Claramunt Santiago , Cracraft Joel
Published: December 2015

Estimates of the timing of evolution of modern birds reveals the influence of paleogeography and paleoclimate on diversification.
An Interspecies Signaling System Mediated by Fusaric Acid Has Parallel Effects on Antifungal Metabolite Production by Pseudomonas protegens Strain Pf-5 and Antibiosis of Fusarium spp
Authors: Quecine Maria Carolina , Kidarsa Teresa A. , Goebel Neal C. , Shaffer Brenda T. , Henkels Marcella D. , Zabriskie T. Mark , Loper Joyce E.
Published: December 2015

Pseudomonas protegens
strain Pf-5 is a rhizosphere bacterium that suppresses soilborne plant diseases and produces at least seven different secondary metabolites with antifungal properties. We derived mutants of Pf-5 with single and multiple mutations in biosynthesis genes for seven antifungal metabolites: 2,4-diacetylphoroglucinol (DAPG), pyrrolnitrin, pyoluteorin, hydrogen cyanide, rhizoxin, orfamide A, and toxoflavin. These mutants were tested for inhibition of the pathogens
Fusarium verticillioides
and
Fusarium oxysporum
f. sp.
pisi
. Rhizoxin, pyrrolnitrin, and DAPG were found to be primarily responsible for fungal antagonism by Pf-5. Previously, other workers showed that the mycotoxin fusaric acid, which is produced by many
Fusarium
species, including
F. verticillioides
, inhibited the production of DAPG by
Pseudomonas
spp. In this study, amendment of culture media with fusaric acid decreased DAPG production, increased pyoluteorin production, and had no consistent influence on pyrrolnitrin or orfamide A production by Pf-5. Fusaric acid also altered the transcription of biosynthetic genes, indicating that the mycotoxin influenced antibiotic production by Pf-5 at the transcriptional level. Addition of fusaric acid to the culture medium reduced antibiosis of
F. verticillioides
by Pf-5 and derivative strains that produce DAPG but had no effect on antibiosis by Pf-5 derivatives that suppressed
F. verticillioides
due to pyrrolnitrin or rhizoxin production. Our results demonstrated the importance of three compounds, rhizoxin, pyrrolnitrin, and DAPG, in suppression of
Fusarium
spp. by Pf-5 and confirmed that an interspecies signaling system mediated by fusaric acid had parallel effects on antifungal metabolite production and antibiosis by the bacterial biological control organism.
Prevalence and Genetic Diversity of Human Sapoviruses in Shellfish from Commercial Production Areas in Galicia, Spain
Authors: Varela Miguel F. , Polo David , Romalde Jesús L.
Published: December 2015

The prevalence of human forms ofSapovirus, an emerging pathogen of human gastroenteritis, was investigated in an 18-month survey from class B mollusc-harvesting areas in two Galician rias (northwest Spain). The detection and quantification ofSapoviruswas performed by reverse transcription-real-time PCR, according to the recently developed standard method ISO/TS 15216-1:2013, and genotyping by reverse transcription-nested PCR. The bivalve species studied were wild and cultured mussels (Mytilus galloprovincialis), clams (Venerupis philippinarumandVenerupis decussata), and cockles (Cerastoderma edule).Sapoviruswas detected in 30 out of 168 samples (17.9%), with cockles being the species with the highest prevalence of positives (28.1%), followed by clams (22.6%), wild mussels (14.3%), and cultured mussels (12.9%). The estuary in the south of the region demonstrated a higher percentage of positive samples (21.8%) than the one in the north (14.4%). Viral contamination levels for the positive samples ranged between 1.9 × 103and 1.4 × 105RNA copies/g of digestive tissue. ThirteenSapovirussequences could be obtained based on partial capsid gene sequence and were classified into four genotypes: GI.1 (2 samples), GI.2 (8 samples), GIV.1 (2 samples), and GV.1 (1 sample).
A 2-Hydroxypyridine Catabolism Pathway in Rhodococcus rhodochrous Strain PY11
Authors: Vaitekūnas Justas , Gasparavičiūtė Renata , Rutkienė Rasa , Tauraitė Daiva , Meškys Rolandas
Published: December 2015

Rhodococcus rhodochrous
PY11 (DSM 101666) is able to use 2-hydroxypyridine as a sole source of carbon and energy. By investigating a gene cluster (
hpo
) from this bacterium, we were able to reconstruct the catabolic pathway of 2-hydroxypyridine degradation. Here, we report that in
Rhodococcus rhodochrous
PY11, the initial hydroxylation of 2-hydroxypyridine is catalyzed by a four-component dioxygenase (HpoBCDF). A product of the dioxygenase reaction (3,6-dihydroxy-1,2,3,6-tetrahydropyridin-2-one) is further oxidized by HpoE to 2,3,6-trihydroxypyridine, which spontaneously forms a blue pigment. In addition, we show that the subsequent 2,3,6-trihydroxypyridine ring opening is catalyzed by the hypothetical cyclase HpoH. The final products of 2-hydroxypyridine degradation in
Rhodococcus rhodochrous
PY11 are ammonium ion and α-ketoglutarate.
Lactobacillus rhamnosus GR-1 Ameliorates Escherichia coli-Induced Inflammation and Cell Damage via Attenuation of ASC-Independent NLRP3 Inflammasome Activation
Authors: Wu Qiong , Liu Ming-Chao , Yang Jun , Wang Jiu-Feng , Zhu Yao-Hong
Published: December 2015

Escherichia coli
is a major environmental pathogen causing bovine mastitis, which leads to mammary tissue damage and cell death. We explored the effects of the probiotic
Lactobacillus rhamnosus
GR-1 on ameliorating
E. coli
-induced inflammation and cell damage in primary bovine mammary epithelial cells (BMECs). Increased Toll-like receptor 4 (TLR4), NOD1, and NOD2 mRNA expression was observed following
E. coli
challenge, but this increase was attenuated by
L. rhamnosus
GR-1 pretreatment. Immunofluorescence and Western blot analyses revealed that
L. rhamnosus
GR-1 pretreatment decreased the
E. coli
-induced increases in the expression of the NOD-like receptor family member pyrin domain-containing protein 3 (NLRP3) and the serine protease caspase 1. However, expression of the adaptor protein apoptosis-associated speck-like protein (ASC, encoded by the
Pycard
gene) was decreased during
E. coli
infection, even with
L. rhamnosus
GR-1 pretreatment. Pretreatment with
L. rhamnosus
GR-1 counteracted the
E. coli
-induced increases in interleukin-1β (IL-1β), -6, -8, and -18 and tumor necrosis factor alpha mRNA expression but upregulated IL-10 mRNA expression. Our data indicate that
L. rhamnosus
GR-1 reduces the adhesion of
E. coli
to BMECs, subsequently ameliorating
E. coli
-induced disruption of cellular morphology and ultrastructure and limiting detrimental inflammatory responses, partly via promoting TLR2 and NOD1 synergism and attenuating ASC-independent NLRP3 inflammasome activation. Although the residual pathogenic activity of
L. rhamnosus
, the dosage regimen, and the means of probiotic supplementation in cattle remain undefined, our data enhance our understanding of the mechanism of action of this candidate probiotic, allowing for development of specific probiotic-based therapies and strategies for preventing pathogenic infection of the bovine mammary gland.
A NewN-Acyl Homoserine Lactone Synthase in an Uncultured Symbiont of the Red Sea Sponge Theonella swinhoei
Authors: Britstein Maya , Devescovi Giulia , Handley Kim M. , Malik Assaf , Haber Markus , Saurav Kumar , Teta Roberta , Costantino Valeria , Burgsdorf Ilia , Gilbert Jack A. , Sher Noa , Venturi Vittorio , Steindler Laura
Published: December 2015

Sponges harbor a remarkable diversity of microbial symbionts in which signal molecules can accumulate and enable cell-cell communication, such as quorum sensing (QS). Bacteria capable of QS were isolated from marine sponges; however, an extremely small fraction of the sponge microbiome is amenable to cultivation. We took advantage of community genome assembly and binning to investigate the uncultured majority of sponge symbionts. We identified a completeN-acyl-homoserine lactone (AHL)-QS system (designated TswIR) and seven partialluxIhomologues in the microbiome ofTheonella swinhoei. The TswIR system was novel and shown to be associated with an alphaproteobacterium of the orderRhodobacterales, here termedRhodobacteralesbacterium TS309. ThetswIgene, when expressed inEscherichia coli, produced three AHLs, two of which were also identified in aT. swinhoeisponge extract. The taxonomic affiliation of the 16S rRNA ofRhodobacteralesbacterium TS309 to a sponge-coral specific clade, its enrichment in sponge versus seawater and marine sediment samples, and the presence of sponge-specific features, such as ankyrin-like domains and tetratricopeptide repeats, indicate a likely symbiotic nature of this bacterium.
Alginate Biosynthesis Factories in Pseudomonas fluorescens: Localization and Correlation with Alginate Production Level
Authors: Maleki Susan , Almaas Eivind , Zotchev Sergey , Valla Svein , Ertesvåg Helga
Published: December 2015

Pseudomonas fluorescens
is able to produce the medically and industrially important exopolysaccharide alginate. The proteins involved in alginate biosynthesis and secretion form a multiprotein complex spanning the inner and outer membranes. In the present study, we developed a method by which the porin AlgE was detected by immunogold labeling and transmission electron microscopy. Localization of the AlgE protein was found to depend on the presence of other proteins in the multiprotein complex. No correlation was found between the number of alginate factories and the alginate production level, nor were the numbers of these factories affected in an
algC
mutant that is unable to produce the precursor needed for alginate biosynthesis. Precursor availability and growth phase thus seem to be the main determinants for the alginate production rate in our strain. Clustering analysis demonstrated that the alginate multiprotein complexes were not distributed randomly over the entire outer cell membrane surface.
A Fivefold Parallelized Biosynthetic Process Secures Chlorination of Armillaria mellea (Honey Mushroom) Toxins
Authors: Wick Jonas , Heine Daniel , Lackner Gerald , Misiek Mathias , Tauber James , Jagusch Hans , Hertweck Christian , Hoffmeister Dirk
Published: December 2015

The basidiomycetous tree pathogen
Armillaria mellea
(honey mushroom) produces a large variety of structurally related antibiotically active and phytotoxic natural products, referred to as the melleolides. During their biosynthesis, some members of the melleolide family of compounds undergo monochlorination of the aromatic moiety, whose biochemical and genetic basis was not known previously. This first study on basidiomycete halogenases presents the biochemical
in vitro
characterization of five flavin-dependent
A. mellea
enzymes (ArmH1 to ArmH5) that were heterologously produced in
Escherichia coli
. We demonstrate that all five enzymes transfer a single chlorine atom to the melleolide backbone. A 5-fold, secured biosynthetic step during natural product assembly is unprecedented. Typically, flavin-dependent halogenases are categorized into enzymes acting on free compounds as opposed to those requiring a carrier-protein-bound acceptor substrate. The enzymes characterized in this study clearly turned over free substrates. Phylogenetic clades of halogenases suggest that all fungal enzymes share an ancestor and reflect a clear divergence between ascomycetes and basidiomycetes.